WorldWideScience

Sample records for central pain mechanisms

  1. Evidence of involvement of central neural mechanisms in generating fibromyalgia pain.

    Science.gov (United States)

    Staud, Roland

    2002-08-01

    Fibromyalgia syndrome (FMS) is characterized by widespread pain, fatigue, sleep abnormalities, and distress. Because FMS lacks consistent evidence of tissue abnormalities, recent investigations have focused on central nervous system mechanisms of pain. Abnormal temporal summation of second pain (wind-up) and central sensitization have been described recently in patients with FMS. Wind-up and central sensitization, which rely on central pain mechanisms, occur after prolonged C-nociceptor input and depend on activation of nociceptor-specific neurons and wide dynamic range neurons in the dorsal horn of the spinal cord. Other abnormal central pain mechanisms recently detected in patients with FMS include diffuse noxious inhibitory controls. These pain inhibitory mechanisms rely on spinal cord and supraspinal systems involving pain facilitatory and pain inhibitory pathways. Brain-imaging techniques that can detect neuronal activation after nociceptive stimuli have provided additional evidence for abnormal central pain mechanisms in FMS. Brain images have corroborated the augmented reported pain experience of patients with fibromyalgia during experimental pain stimuli. In addition, thalamic activity, which contributes significantly to pain processing, was decreased in fibromyalgia. However, central pain mechanisms of fibromyalgia may not depend exclusively on neuronal activation. Neuroglial activation has been found to play an important role in the induction and maintenance of chronic pain. These findings may have important implications for future research and the treatment of fibromyalgia pain.

  2. Central pain.

    Science.gov (United States)

    Singh, Supreet

    2014-12-01

    Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The topic addressed in this issue is central pain, a neuropathic pain syndrome caused by a lesion in the brain or spinal cord that sensitizes one's perception of pain. It is a debilitating condition caused by various diseases such as multiple sclerosis, strokes, spinal cord injuries, or brain tumors. Varied symptoms and the use of pharmacological medicines and nonpharmacological therapies will be addressed.

  3. Central Pain Mechanisms and Novel Therapeutic Strategies in a Model of Closed Head Injury

    Science.gov (United States)

    2015-10-01

    AD_________________ Award Number: W81XWH-14-1-0594 TITLE: Central Pain Mechanisms and Novel Therapeutic Strategies in a Model of Closed Head...30Sep2014-29Sep2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Central Pain Mechanisms and Novel Therapeutic Strategies in a Model of Closed Head...was to determine the pattern of inflammation-induced sensitization of the central trigeminal pain neurons, and if sensitization is detectable by

  4. [The trigemino-cervical complex. Integration of peripheral and central pain mechanisms in primary headache syndromes].

    Science.gov (United States)

    Busch, V; Frese, A; Bartsch, T

    2004-10-01

    The activation of the trigeminal nociceptive system is the neural substrate of pain in primary headache syndromes such as migraine and cluster headache. The nociceptive inflow from the meninges to the spinal cord is relayed in brainstem neurones of the trigemino-cervical complex (TCC). Two important mechanisms of pain transmission are reviewed: convergence of nociceptive trigeminal and cervical afferents and sensitization of trigemino-cervical neurones. These mechanisms have clinical correlates such as hyperalgesia, allodynia, spread and referral of pain to trigeminal or cervical dermatomes. Neurones in the TCC are subject to a modulation of pain-modulatory circuits in the brainstem such as the periaqueductal grey (PAG). Recent experimental and clinical findings of a modulation of these pain processes are discussed. The review focuses on TCC neurones as integrative relay neurones between peripheral and central pain mechanisms. The understanding of these mechanisms has implications for the understanding of the clinical phenomenology in primary headache syndromes and the development of therapeutical options.

  5. Central Neuropathic Pain Syndromes.

    Science.gov (United States)

    Watson, James C; Sandroni, Paola

    2016-03-01

    Chronic pain is common in patients with neurologic complications of a central nervous system insult such as stroke. The pain is most commonly musculoskeletal or related to obligatory overuse of neurologically unaffected limbs. However, neuropathic pain can result directly from the central nervous system injury. Impaired sensory discrimination can make it challenging to differentiate central neuropathic pain from other pain types or spasticity. Central neuropathic pain may also begin months to years after the injury, further obscuring recognition of its association with a past neurologic injury. This review focuses on unique clinical features that help distinguish central neuropathic pain. The most common clinical central pain syndromes-central poststroke pain, multiple sclerosis-related pain, and spinal cord injury-related pain-are reviewed in detail. Recent progress in understanding of the pathogenesis of central neuropathic pain is reviewed, and pharmacological, surgical, and neuromodulatory treatments of this notoriously difficult to treat pain syndrome are discussed.

  6. Bilateral widespread mechanical pain sensitivity in carpal tunnel syndrome: evidence of central processing in unilateral neuropathy.

    Science.gov (United States)

    Fernández-de-las-Peñas, César; de la Llave-Rincón, Ana Isabel; Fernández-Carnero, Josué; Cuadrado, María Luz; Arendt-Nielsen, Lars; Pareja, Juan A

    2009-06-01

    The aim of this study was to investigate whether bilateral widespread pressure hypersensitivity exists in patients with unilateral carpal tunnel syndrome. A total of 20 females with carpal tunnel syndrome (aged 22-60 years), and 20 healthy matched females (aged 21-60 years old) were recruited. Pressure pain thresholds were assessed bilaterally over median, ulnar, and radial nerve trunks, the C5-C6 zygapophyseal joint, the carpal tunnel and the tibialis anterior muscle in a blinded design. The results showed that pressure pain threshold levels were significantly decreased bilaterally over the median, ulnar, and radial nerve trunks, the carpal tunnel, the C5-C6 zygapophyseal joint, and the tibialis anterior muscle in patients with unilateral carpal tunnel syndrome as compared to healthy controls (all, P < 0.001). Pressure pain threshold was negatively correlated to both hand pain intensity and duration of symptoms (all, P < 0.001). Our findings revealed bilateral widespread pressure hypersensitivity in subjects with carpal tunnel syndrome, which suggest that widespread central sensitization is involved in patients with unilateral carpal tunnel syndrome. The generalized decrease in pressure pain thresholds associated with pain intensity and duration of symptoms supports a role of the peripheral drive to initiate and maintain central sensitization. Nevertheless, both central and peripheral sensitization mechanisms are probably involved at the same time in carpal tunnel syndrome.

  7. The role of CGRP in peripheral and central pain mechanisms including migraine.

    Science.gov (United States)

    Iyengar, Smriti; Ossipov, Michael H; Johnson, Kirk W

    2016-12-29

    Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide found primarily in the C and Aδ sensory fibers arising from the dorsal root and trigeminal ganglia, as well as the central nervous system. CGRP was found to play important roles in cardiovascular, digestive, and sensory functions. Although the vasodilatory properties of CGRP are well documented, its somatosensory function regarding modulation of neuronal sensitization and of enhanced pain has received considerable attention recently. Growing evidence indicates that CGRP plays a key role in the development of peripheral sensitization and the associated enhanced pain. CGRP is implicated in the development of neurogenic inflammation and it is upregulated in conditions of inflammatory and neuropathic pain. It is most likely that CGRP facilitates nociceptive transmission and contributes to the development and maintenance of a sensitized, hyper-responsive state not only of the primary afferent sensory neurons, but also of the second-order pain transmission neurons within the CNS, thus contributing to central sensitization as well. The maintenance of a sensitized neuronal condition is believed to be an important factor underlying migraine. Recent successful clinical studies have shown that blocking the function of CGRP can alleviate migraine. However, the mechanisms through which CGRP may contribute to migraine are still not fully understood. We reviewed the role of CGRP in primary afferents, the dorsal root ganglion, and in the trigeminal system as well as its role in peripheral and central sensitization and its potential contribution to pain processing and to migraine.

  8. The Central Analgesic Mechanism of YM-58483 in Attenuating Neuropathic Pain in Rats.

    Science.gov (United States)

    Qi, Zeyou; Wang, Yaping; Zhou, Haocheng; Liang, Na; Yang, Lin; Liu, Lei; Zhang, Wei

    2016-10-01

    Calcium channel antagonists are commonly used to treat neuropathic pain. Their analgesic effects rely on inhibiting long-term potentiation, and neurotransmitters release in the spinal cord. Store-operated Ca(2+)channels (SOCCs) are highly Ca(2+)-selective cation channels broadly expressed in non-excitable cells and some excitable cells. Recent studies have shown that the potent inhibitor of SOCCs, YM-58483, has analgesic effects on neuropathic pain, but its mechanism is unclear. This experiment performed on spinal nerve ligation (SNL)-induced neuropathic pain model in rats tries to explore the mechanism, whereby YM-58483 attenuates neuropathic pain. The left L5 was ligated to produce the SNL neuropathic pain model in male Sprague-Dawley rats. The withdrawal threshold of rats was measured by the up-down method and Hargreaves' method before and after intrathecal administration of YM-58483 and vehicle. The SOCCs in the spinal dorsal horn were located by immunofluorescence. The expression of phosphorylated ERK and phosphorylated CREB, CD11b, and GFAP proteins in spinal level was tested by Western blot, while the release of proinflammatory cytokines (IL-1β, TNF-α, PGE2) was measured by enzyme-linked immunosorbent assay (ELISA). Intrathecal YM-58483 at the concentration of 300 μM (1.5 nmol) and 1000 μM (10 nmol) produced a significant central analgesic effect on the SNL rats, compared with control + vehicle (n = 7, P pain, compared with normal + saline (P  0.05). YM-58483 also inhibited the release of spinal cord IL-1β, TNF-α, and PGE2, compared with control + vehicle (n = 5, #P central ERK/CREB signaling in the neurons and decreasing central IL-1β, TNF-α, and PGE2 release to reduce neuronal excitability in the spinal dorsal horn of the SNL rats.

  9. Central Pain Syndrome

    Science.gov (United States)

    ... or hands. Central pain syndrome often begins shortly after the causative injury or damage, but may be delayed by months or even years, especially if it is related to post-stroke pain. × Definition Central pain syndrome is a neurological ...

  10. The role of calcitonin gene–related peptide in peripheral and central pain mechanisms including migraine

    Science.gov (United States)

    Iyengar, Smriti; Ossipov, Michael H.; Johnson, Kirk W.

    2017-01-01

    Abstract Calcitonin gene–related peptide (CGRP) is a 37-amino acid peptide found primarily in the C and Aδ sensory fibers arising from the dorsal root and trigeminal ganglia, as well as the central nervous system. Calcitonin gene–related peptide was found to play important roles in cardiovascular, digestive, and sensory functions. Although the vasodilatory properties of CGRP are well documented, its somatosensory function regarding modulation of neuronal sensitization and of enhanced pain has received considerable attention recently. Growing evidence indicates that CGRP plays a key role in the development of peripheral sensitization and the associated enhanced pain. Calcitonin gene–related peptide is implicated in the development of neurogenic inflammation and it is upregulated in conditions of inflammatory and neuropathic pain. It is most likely that CGRP facilitates nociceptive transmission and contributes to the development and maintenance of a sensitized, hyperresponsive state not only of the primary afferent sensory neurons but also of the second-order pain transmission neurons within the central nervous system, thus contributing to central sensitization as well. The maintenance of a sensitized neuronal condition is believed to be an important factor underlying migraine. Recent successful clinical studies have shown that blocking the function of CGRP can alleviate migraine. However, the mechanisms through which CGRP may contribute to migraine are still not fully understood. We reviewed the role of CGRP in primary afferents, the dorsal root ganglion, and in the trigeminal system as well as its role in peripheral and central sensitization and its potential contribution to pain processing and to migraine. PMID:28301400

  11. The role of calcitonin gene-related peptide in peripheral and central pain mechanisms including migraine.

    Science.gov (United States)

    Iyengar, Smriti; Ossipov, Michael H; Johnson, Kirk W

    2017-04-01

    Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide found primarily in the C and Aδ sensory fibers arising from the dorsal root and trigeminal ganglia, as well as the central nervous system. Calcitonin gene-related peptide was found to play important roles in cardiovascular, digestive, and sensory functions. Although the vasodilatory properties of CGRP are well documented, its somatosensory function regarding modulation of neuronal sensitization and of enhanced pain has received considerable attention recently. Growing evidence indicates that CGRP plays a key role in the development of peripheral sensitization and the associated enhanced pain. Calcitonin gene-related peptide is implicated in the development of neurogenic inflammation and it is upregulated in conditions of inflammatory and neuropathic pain. It is most likely that CGRP facilitates nociceptive transmission and contributes to the development and maintenance of a sensitized, hyperresponsive state not only of the primary afferent sensory neurons but also of the second-order pain transmission neurons within the central nervous system, thus contributing to central sensitization as well. The maintenance of a sensitized neuronal condition is believed to be an important factor underlying migraine. Recent successful clinical studies have shown that blocking the function of CGRP can alleviate migraine. However, the mechanisms through which CGRP may contribute to migraine are still not fully understood. We reviewed the role of CGRP in primary afferents, the dorsal root ganglion, and in the trigeminal system as well as its role in peripheral and central sensitization and its potential contribution to pain processing and to migraine.

  12. Electroacupuncture in conscious free-moving mice reduces pain by ameliorating peripheral and central nociceptive mechanisms

    Science.gov (United States)

    Wang, Ying; Lei, Jianxun; Gupta, Mihir; Peng, Fei; Lam, Sarah; Jha, Ritu; Raduenz, Ellis; Beitz, Al J.; Gupta, Kalpna

    2016-01-01

    Integrative approaches such as electroacupuncture, devoid of drug effects are gaining prominence for treating pain. Understanding the mechanisms of electroacupuncture induced analgesia would benefit chronic pain conditions such as sickle cell disease (SCD), for which patients may require opioid analgesics throughout life. Mouse models are instructive in developing a mechanistic understanding of pain, but the anesthesia/restraint required to administer electroacupuncture may alter the underlying mechanisms. To overcome these limitations, we developed a method to perform electroacupuncture in conscious, freely moving, unrestrained mice. Using this technique we demonstrate a significant analgesic effect in transgenic mouse models of SCD and cancer as well as complete Freund’s adjuvant-induced pain. We demonstrate a comprehensive antinociceptive effect on mechanical, cold and deep tissue hyperalagesia in both genders. Interestingly, individual mice showed a variable response to electroacupuncture, categorized into high-, moderate-, and non-responders. Mechanistically, electroacupuncture significantly ameliorated inflammatory and nociceptive mediators both peripherally and centrally in sickle mice correlative to the antinociceptive response. Application of sub-optimal doses of morphine in electroacupuncture-treated moderate-responders produced equivalent antinociception as obtained in high-responders. Electroacupuncture in conscious freely moving mice offers an effective approach to develop a mechanism-based understanding of analgesia devoid of the influence of anesthetics or restraints. PMID:27687125

  13. The Discriminative validity of "nociceptive," "peripheral neuropathic," and "central sensitization" as mechanisms-based classifications of musculoskeletal pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-02-01

    OBJECTIVES: Empirical evidence of discriminative validity is required to justify the use of mechanisms-based classifications of musculoskeletal pain in clinical practice. The purpose of this study was to evaluate the discriminative validity of mechanisms-based classifications of pain by identifying discriminatory clusters of clinical criteria predictive of "nociceptive," "peripheral neuropathic," and "central sensitization" pain in patients with low back (+\\/- leg) pain disorders. METHODS: This study was a cross-sectional, between-patients design using the extreme-groups method. Four hundred sixty-four patients with low back (+\\/- leg) pain were assessed using a standardized assessment protocol. After each assessment, patients\\' pain was assigned a mechanisms-based classification. Clinicians then completed a clinical criteria checklist indicating the presence\\/absence of various clinical criteria. RESULTS: Multivariate analyses using binary logistic regression with Bayesian model averaging identified a discriminative cluster of 7, 3, and 4 symptoms and signs predictive of a dominance of "nociceptive," "peripheral neuropathic," and "central sensitization" pain, respectively. Each cluster was found to have high levels of classification accuracy (sensitivity, specificity, positive\\/negative predictive values, positive\\/negative likelihood ratios). DISCUSSION: By identifying a discriminatory cluster of symptoms and signs predictive of "nociceptive," "peripheral neuropathic," and "central" pain, this study provides some preliminary discriminative validity evidence for mechanisms-based classifications of musculoskeletal pain. Classification system validation requires the accumulation of validity evidence before their use in clinical practice can be recommended. Further studies are required to evaluate the construct and criterion validity of mechanisms-based classifications of musculoskeletal pain.

  14. PROTEIN KINASES AND CENTRAL SENSITIZATION OF SPINAL DORSAL HORN NEURONS:CENTRAL MECHANISMS OF PAIN

    Institute of Scientific and Technical Information of China (English)

    QING LIN

    2003-01-01

    @@ The enhanced responsiveness of spinal dorsal horn neurons, including spinothalamic tract (STT) cells, that follows peripheral tissue injury or inflammation is thought to underlie the development of secondary hyperalgesia and allodynia and is referred to as "central sensitization" because the increases in excitability do not appear to depend on continued activity of peripheral nociceptors.

  15. Imaging central pain syndromes.

    Science.gov (United States)

    Veldhuijzen, Dieuwke S; Greenspan, Joel D; Kim, Jong H; Coghill, Robert C; Treede, Rolf-Detlef; Ohara, Shinji; Lenz, Frederick A

    2007-06-01

    Anatomic, functional, and neurochemical imaging studies have provided new investigative tools in the study of central pain. High-resolution imaging studies allow for precise determination of lesion location, whereas functional neuroimaging studies measure pathophysiologic consequences of injury to the central nervous system. Additionally, magnetic resonance spectroscopy evaluates lesion-induced neurochemical changes in specific brain regions that may be related to central pain. The small number of studies to date precludes definitive conclusions, but the recent findings provide information that either supports or refutes current hypotheses and can serve to generate new ideas.

  16. Investigation of Central Pain Processing in Post-Operative Shoulder Pain and Disability

    OpenAIRE

    Valencia, Carolina; Fillingim, Roger B.; Bishop, Mark; Wu, Samuel S.; Wright, Thomas W.; Moser, Michael; Farmer, Kevin; George, Steven Z.

    2014-01-01

    Measures of central pain processing like conditioned pain modulation (CPM), and suprathreshold heat pain response (SHPR) have been described to assess different components of central pain modulatory mechanisms. Central pain processing potentially play a role in the development of postsurgical pain, however, the role of CPM and SHPR in explaining postoperative clinical pain and disability is still unclear.

  17. Mechanisms-based classifications of musculoskeletal pain: part 1 of 3: symptoms and signs of central sensitisation in patients with low back (± leg) pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-08-01

    As a mechanisms-based classification of pain \\'central sensitisation pain\\' (CSP) refers to pain arising from a dominance of neurophysiological dysfunction within the central nervous system. Symptoms and signs associated with an assumed dominance of CSP in patients attending for physiotherapy have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of CSP in patients with low back (± leg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (± leg) pain were assessed using a standardised assessment protocol. Patients\\' pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist specifying the presence or absence of various clinical criteria. A binary logistic regression analysis with Bayesian model averaging identified a cluster of three symptoms and one sign predictive of CSP, including: \\'Disproportionate, non-mechanical, unpredictable pattern of pain provocation in response to multiple\\/non-specific aggravating\\/easing factors\\

  18. Neuroinflammatory contributions to pain after SCI: roles for central glial mechanisms and nociceptor-mediated host defense.

    Science.gov (United States)

    Walters, Edgar T

    2014-08-01

    Neuropathic pain after spinal cord injury (SCI) is common, often intractable, and can be severely debilitating. A number of mechanisms have been proposed for this pain, which are discussed briefly, along with methods for revealing SCI pain in animal models, such as the recently applied conditioned place preference test. During the last decade, studies of animal models have shown that both central neuroinflammation and behavioral hypersensitivity (indirect reflex measures of pain) persist chronically after SCI. Interventions that reduce neuroinflammation have been found to ameliorate pain-related behavior, such as treatment with agents that inhibit the activation states of microglia and/or astroglia (including IL-10, minocycline, etanercept, propentofylline, ibudilast, licofelone, SP600125, carbenoxolone). Reversal of pain-related behavior has also been shown with disruption by an inhibitor (CR8) and/or genetic deletion of cell cycle-related proteins, deletion of a truncated receptor (trkB.T1) for brain-derived neurotrophic factor (BDNF), or reduction by antisense knockdown or an inhibitor (AMG9810) of the activity of channels (TRPV1 or Nav1.8) important for electrical activity in primary nociceptors. Nociceptor activity is known to drive central neuroinflammation in peripheral injury models, and nociceptors appear to be an integral component of host defense. Thus, emerging results suggest that spinal and systemic effects of SCI can activate nociceptor-mediated host defense responses that interact via neuroinflammatory signaling with complex central consequences of SCI to drive chronic pain. This broader view of SCI-induced neuroinflammation suggests new targets, and additional complications, for efforts to develop effective treatments for neuropathic SCI pain.

  19. Self-reported pain severity, quality of life, disability, anxiety and depression in patients classified with 'nociceptive', 'peripheral neuropathic' and 'central sensitisation' pain. The discriminant validity of mechanisms-based classifications of low back (±leg) pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-04-01

    Evidence of validity is required to support the use of mechanisms-based classifications of pain clinically. The purpose of this study was to evaluate the discriminant validity of \\'nociceptive\\' (NP), \\'peripheral neuropathic\\' (PNP) and \\'central sensitisation\\' (CSP) as mechanisms-based classifications of pain in patients with low back (±leg) pain by evaluating the extent to which patients classified in this way differ from one another according to health measures associated with various dimensions of pain. This study employed a cross-sectional, between-subjects design. Four hundred and sixty-four patients with low back (±leg) pain were assessed using a standardised assessment protocol. Clinicians classified each patient\\'s pain using a mechanisms-based classification approach. Patients completed a number of self-report measures associated with pain severity, health-related quality of life, functional disability, anxiety and depression. Discriminant validity was evaluated using a multivariate analysis of variance. There was a statistically significant difference between pain classifications on the combined self-report measures, (p = .001; Pillai\\'s Trace = .33; partial eta squared = .16). Patients classified with CSP (n = 106) reported significantly more severe pain, poorer general health-related quality of life, and greater levels of back pain-related disability, depression and anxiety compared to those classified with PNP (n = 102) and NP (n = 256). A similar pattern was found in patients with PNP compared to NP. Mechanisms-based pain classifications may reflect meaningful differences in attributes underlying the multidimensionality of pain. Further studies are required to evaluate the construct and criterion validity of mechanisms-based classifications of musculoskeletal pain.

  20. Craniofacial Pain: Brainstem Mechanisms

    Directory of Open Access Journals (Sweden)

    Barry J Sessle

    1996-01-01

    Full Text Available This article reviews recent research advances in animals that have identified critical neural elements in the brainstem receiving and transmitting craniofacial nociceptive inputs, as well as some of the mechanisms involved in the modulation and plasticity of nociceptive transmission. Nociceptive neurones in the trigeminal (V brainstem sensory nuclear complex can be classified as nociceptive-specific (NS or wide dynamic range (WDR. Some of these neurones respond exclusively to sensory inputs evoked by stimulation of facial skin or oral mucosa and have features suggesting that they are critical neural elements involved in the ability to localize an acute superficial pain and sense its intensity and duration. Many of the V brainstem nociceptive neurones, however, receive convergent inputs from afferents supplying deep craniofacial tissues (eg, dural vessel, muscle and skin or mucosa. These neurones are likely involved in deep pain, including headache, because few nociceptive neurones receive inputs exclusively from afferents supplying these tissues. These extensive convergent input patterns also appear to be important factors in pain spread and referral, and in central mechanisms underlying neuroplastic changes in V neuronal properties that may occur with injury and inflammation. For example, application of the small fibre excitant and inflammatory irritant mustard oil into the temporomandibular joint, masseter or tongue musculature induces a prolonged but reversible enhancement of responses to cutaneous and deep afferent inputs of most WDR and NS neurones. These effects may be accompanied by increased electromyographic activity reflexly induced in the masticatory muscles by mustard oil, and involve endogenous N-methyl-D-aspartate and opioid neurochemical mechanisms. Such peripherally induced modulation of brainstem nociceptive neuronal properties reflects the functional plasticity of the central V system, and may be involved in the development of

  1. Central adaptation of pain perception in response to rehabilitation of musculoskeletal pain

    DEFF Research Database (Denmark)

    Andersen, Lars L; Andersen, Christoffer H; Sundstrup, Emil

    2012-01-01

    Understanding the mechanisms of long-standing musculoskeletal pain and adaptations in response to physical rehabilitation is important for developing optimal treatment strategies. The influence of central adaptations of pain perception in response to rehabilitation of musculoskeletal pain remains...

  2. The characteristics of chronic central pain after traumatic brain injury.

    Science.gov (United States)

    Ofek, Hadas; Defrin, Ruth

    2007-10-01

    Central pain following traumatic brain injury (TBI) has not been studied in depth. Our purpose was to conduct a systematic study of patients with TBI suffering from chronic central pain, and to describe the characteristics of the central pain. Groups were TBI patients with (TBIP) and without central pain (TBINP) and healthy controls. TBI patients with other pain mechanisms were excluded from the study. Participants underwent quantitative somatosensory testing in the painful and pain-free body regions. Thresholds for warmth, cold, heat-pain, touch and graphesthesia were measured and pathologically evoked pain (allodynia, hyperpathia and wind-up pain) evaluated. Chronic pain was mapped and characterized. Chronic pain developed at a relatively late onset (6.6+/-9 months) was almost exclusively unilateral and reported as pricking, throbbing and burning. Although both TBIP and TBINP exhibited a significant reduction in thermal and tactile sensations compared to controls, thermal sensations in the painful regions of TBIP were significantly more impaired than pain-free regions in the same patients (p<0.01) and in TBINP (p<0.01). Painful regions also exhibited very high rates of allodynia, hyperpathia and exaggerated wind-up. The characteristics of the chronic pain resembled those of other central pain patients although TBIP displayed several unique features. The sensory profile indicated that damage to the pain and temperature systems is a necessary but not sufficient condition for the development of chronic central pain following TBI. Neuronal hyperexcitability may be a contributing factor to the chronic pain.

  3. Pain and nociception: mechanisms of cancer-induced bone pain.

    Science.gov (United States)

    Falk, Sarah; Dickenson, Anthony H

    2014-06-01

    Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic. As detection and survival among patients with cancer have improved, pain has become an increasing challenge, because traditional therapies are often only partially effective. Until recently, knowledge of cancer pain mechanisms was poor compared with understanding of neuropathic and inflammatory pain states. We now view cancer-induced bone pain as a complex pain state involving components of both inflammatory and neuropathic pain but also exhibiting elements that seem unique to cancer pain. In addition, the pain state is often unpredictable, and the intensity of the pain is highly variable, making it difficult to manage. The establishment of translational animal models has started to reveal some of the molecular components involved in cancer pain. We present the essential pharmacologic and neurobiologic mechanisms involved in the generation and continuance of cancer-induced bone pain and discuss these in the context of understanding and treating patients. We discuss changes in peripheral signaling in the area of tumor growth, examine spinal cord mechanisms of sensitization, and finally address central processing. Our aim is to provide a mechanistic background for the sensory characteristics of cancer-induced bone pain as a basis for better understanding and treating this condition.

  4. Mechanisms of cardiac pain.

    Science.gov (United States)

    Foreman, Robert D; Garrett, Kennon M; Blair, Robert W

    2015-04-01

    Angina pectoris is cardiac pain that typically is manifested as referred pain to the chest and upper left arm. Atypical pain to describe localization of the perception, generally experienced more by women, is referred to the back, neck, and/or jaw. This article summarizes the neurophysiological and pharmacological mechanisms for referred cardiac pain. Spinal cardiac afferent fibers mediate typical anginal pain via pathways from the spinal cord to the thalamus and ultimately cerebral cortex. Spinal neurotransmission involves substance P, glutamate, and transient receptor potential vanilloid-1 (TRPV1) receptors; release of neurokinins such as nuclear factor kappa b (NF-kb) in the spinal cord can modulate neurotransmission. Vagal cardiac afferent fibers likely mediate atypical anginal pain and contribute to cardiac ischemia without accompanying pain via relays through the nucleus of the solitary tract and the C1-C2 spinal segments. The psychological state of an individual can modulate cardiac nociception via pathways involving the amygdala. Descending pathways originating from nucleus raphe magnus and the pons also can modulate cardiac nociception. Sensory input from other visceral organs can mimic cardiac pain due to convergence of this input with cardiac input onto spinothalamic tract neurons. Reduction of converging nociceptive input from the gallbladder and gastrointestinal tract can diminish cardiac pain. Much work remains to be performed to discern the interactions among complex neural pathways that ultimately produce or do not produce the sensations associated with cardiac pain.

  5. Painful neuropathy: Mechanisms.

    Science.gov (United States)

    Lee-Kubli, Corinne A; Calcutt, Nigel A

    2014-01-01

    Painful neuropathy, like the other complications of diabetes, is a growing healthcare concern. Unfortunately, current treatments are of variable efficacy and do not target underlying pathogenic mechanisms, in part because these mechanisms are not well defined. Rat and mouse models of type 1 diabetes are frequently used to study diabetic neuropathy, with rats in particular being consistently reported to show allodynia and hyperalgesia. Models of type 2 diabetes are being used with increasing frequency, but the current literature on the progression of indices of neuropathic pain is variable and relatively few therapeutics have yet been developed in these models. While evidence for spontaneous pain in rodent models is sparse, measures of evoked mechanical, thermal and chemical pain can provide insight into the pathogenesis of the condition. The stocking and glove distribution of pain tantalizingly suggests that the generator site of neuropathic pain is found within the peripheral nervous system. However, emerging evidence demonstrates that amplification in the spinal cord, via spinal disinhibition and neuroinflammation, and also in the brain, via enhanced thalamic activity or decreased cortical inhibition, likely contribute to the pathogenesis of painful diabetic neuropathy. Several potential therapeutic strategies have emerged from preclinical studies, including prophylactic treatments that intervene against underlying mechanisms of disease, treatments that prevent gains of nociceptive function, treatments that suppress enhancements of nociceptive function, and treatments that impede normal nociceptive mechanisms. Ongoing challenges include unraveling the complexity of underlying pathogenic mechanisms, addressing the potential disconnect between the perceived location of pain and the actual pain generator and amplifier sites, and finding ways to identify which mechanisms operate in specific patients to allow rational and individualized choice of targeted therapies.

  6. Mechanisms of chronic pain from whiplash injury.

    Science.gov (United States)

    Davis, Charles G

    2013-02-01

    This article is to provide insights into the mechanisms underlying chronic pain from whiplash injury. Studies show that injury produces plasticity changes of different neuronal structures that are responsible for amplification of nociception and exaggerated pain responses. There is consistent evidence for hypersensitivity of the central nervous system to sensory stimulation in chronic pain after whiplash injury. Tissue damage, detected or not by the available diagnostic methods, is probably the main determinant of central hypersensitivity. Different mechanisms underlie and co-exist in the chronic whiplash condition. Spinal cord hyperexcitability in patients with chronic pain after whiplash injury can cause exaggerated pain following low intensity nociceptive or innocuous peripheral stimulation. Spinal hypersensitivity may explain pain in the absence of detectable tissue damage. Whiplash is a heterogeneous condition with some individuals showing features suggestive of neuropathic pain. A predominantly neuropathic pain component is related to a higher pain/disability level.

  7. Human psychophysics and rodent spinal neurones exhibit peripheral and central mechanisms of inflammatory pain in the UVB and UVB heat rekindling models.

    Science.gov (United States)

    O'Neill, Jessica; Sikandar, Shafaq; McMahon, Stephen B; Dickenson, Anthony H

    2015-09-01

    Translational research is key to bridging the gaps between preclinical findings and the patients, and a translational model of inflammatory pain will ideally induce both peripheral and central sensitisation, more effectively mimicking clinical pathophysiology in some chronic inflammatory conditions. We conducted a parallel investigation of two models of inflammatory pain, using ultraviolet B (UVB) irradiation alone and UVB irradiation with heat rekindling. We used rodent electrophysiology and human quantitative sensory testing to characterise nociceptive processing in the peripheral and central nervous systems in both models. In both species, UVB irradiation produces peripheral sensitisation measured as augmented evoked activity of rat dorsal horn neurones and increased perceptual responses of human subjects to mechanical and thermal stimuli. In both species, UVB with heat rekindling produces central sensitisation. UVB irradiation alone and UVB with heat rekindling are translational models of inflammation that produce peripheral and central sensitisation, respectively. The predictive value of laboratory models for human pain processing is crucial for improving translational research. The discrepancy between peripheral and central mechanisms of pain is an important consideration for drug targets, and here we describe two models of inflammatory pain that involve ultraviolet B (UVB) irradiation, which can employ peripheral and central sensitisation to produce mechanical and thermal hyperalgesia in rats and humans. We use electrophysiology in rats to measure the mechanically- and thermally-evoked activity of rat spinal neurones and quantitative sensory testing to assess human psychophysical responses to mechanical and thermal stimulation in a model of UVB irradiation and in a model of UVB irradiation with heat rekindling. Our results demonstrate peripheral sensitisation in both species driven by UVB irradiation, with a clear mechanical and thermal hypersensitivity of

  8. Central or peripheral delivery of an adenosine A1 receptor agonist improves mechanical allodynia in a mouse model of painful diabetic neuropathy.

    Science.gov (United States)

    Katz, N K; Ryals, J M; Wright, D E

    2015-01-29

    Diabetic peripheral neuropathy is a common complication of diabetes mellitus, and a significant proportion of individuals suffer debilitating pain that significantly affects their quality of life. Unfortunately, symptomatic treatment options have limited efficacy, and often carry significant risk of systemic adverse effects. Activation of the adenosine A1 receptor (A1R) by the analgesic small molecule adenosine has been shown to have antinociceptive benefits in models of inflammatory and neuropathic pain. The current study used a mouse model of painful diabetic neuropathy to determine the effect of diabetes on endogenous adenosine production, and if central or peripheral delivery of adenosine receptor agonists could alleviate signs of mechanical allodynia in diabetic mice. Diabetes was induced using streptozocin in male A/J mice. Mechanical withdrawal thresholds were measured weekly to characterize neuropathy phenotype. Hydrolysis of AMP into adenosine by ectonucleotidases was determined in the dorsal root ganglia (DRG) and spinal cord at 8 weeks post-induction of diabetes. AMP, adenosine and the specific A1R agonist, N(6)-cyclopentyladenosine (CPA), were administered both centrally (intrathecal) and peripherally (intraplantar) to determine the effect of activation of adenosine receptors on mechanical allodynia in diabetic mice. Eight weeks post-induction, diabetic mice displayed significantly decreased hydrolysis of extracellular AMP in the DRG; at this same time, diabetic mice displayed significantly decreased mechanical withdrawal thresholds compared to nondiabetic controls. Central delivery AMP, adenosine and CPA significantly improved mechanical withdrawal thresholds in diabetic mice. Surprisingly, peripheral delivery of CPA also improved mechanical allodynia in diabetic mice. This study provides new evidence that diabetes significantly affects endogenous AMP hydrolysis, suggesting that altered adenosine production could contribute to the development of

  9. Mechanisms of postoperative pain

    Institute of Scientific and Technical Information of China (English)

    YUE Yun

    2007-01-01

    @@ The practice of modern anaesthesiology has extended into perioperative medicine. Due to their expertise in analgesic drug pharmacology and peripheral nerve blocking, anaesthesiologists have pioneered in the management of acute postoperative pain. Effective postoperative analgesia reduces the incidence of postoperative chronic pain, improves the functioning of organs following surgery and shortens the hospital stay.1,2 Although a variety of analgesic techniques and preventative approaches are at the disposal of modem aneasthesiologists, including patient controlled epidural analgesia (PCEA), patient controlled intravenous analgesia, multimodal analgesia and pre-empty analgesia.Despite this array of strategies, these predominantly opioid based techniques are still limited by side-effects such as vomiting, nausea, itching and urinary retention.To optimize further the management of acute postoperative pain, basic mechanisms of postoperative pain must be explored and new treatments must continue to be developed.

  10. Altered central sensitization and pain modulation in the CNS in chronic joint pain

    DEFF Research Database (Denmark)

    Arendt-Nielsen, Lars; Skou, Søren Thorgaard; Nielsen, Thomas Arendt

    2015-01-01

    and central pain mechanisms are not fully understood, and safe and efficient analgesic drugs are not available. The pain associated with joint pain is highly individual, and features from radiological imaging have not demonstrated robust associations with the pain manifestations. In recent years, a variety......Musculoskeletal pain disorders are the second largest contributor to global disability underlining the significance of effective treatments. However, treating chronic musculoskeletal pain, and chronic joint pain (osteoarthritis (OA)) in particular, is challenging as the underlying peripheral...... of human quantitative pain assessment tools (quantitative sensory testing (QST)) have been developed providing new opportunities for profiling patients and reaching a greater understanding of the mechanisms involved in chronic joint pain. As joint pain is a complex interaction between many different pain...

  11. CENTRAL MECHANISMS OF ACUPUNCTURE ANALGESIA

    Directory of Open Access Journals (Sweden)

    Eman S. Mansour

    2015-12-01

    Full Text Available Background: Acupuncture is an component of traditional Chinese medicine (TCM that has been used for three thousand years to treat diseases and relieve pain. Pain is found to be the most common reason for people to use acupuncture. Due to recent scientific findings, acupuncture treatment has been accepted worldwide. Numerous trials have been conducted especially in analgesia. The mechanisms of acupuncture analgesia has been widely investigated, however, the underlying mechanism still not clear. This article summarizes the central mechanisms of acupuncture analgesia and reviews recent studies on the topic. Method: We have focused on examining the recent literature on acupuncture analgesia. The central mechanisms of acupuncture analgesia and reviews recent studies on the topic. We focused on the studies related to central mechanisms of acupuncture analgesia from these aspects: (neurophysiology, neurochemistry and neuroanatomy. Result: The result revealed that acupuncture act on various parts of the central nervous system, including the spinal cord, brain stem, cerebral ganglia and cerebral cortex to alleviate pain. The central mechanisms underlying the effects of acupuncture include neurohumors and neurotransmitters, which are involved in analgesia. At spinal level, Spinal opioids, glutamate, norepinephrine and serotonin are the key elements acupuncture-induced analgesia. At brain level, Endogenous opioid peptides, limbic system play essential roles in mediating the analgesia. Conclusion: Acupuncture is an effective approach to pain management. There is good evidence in both experimental and clinical research that supports acupuncture efficacy in management of chronic pain through central nervous system. Acupuncture should be strongly used as a part of pain management plans. This work helps in improving our understanding of the scientific basis underlying acupuncture analgesia.

  12. The nature and course of sensory changes following spinal cord injury: predictive properties and implications on the mechanism of central pain.

    Science.gov (United States)

    Zeilig, Gabi; Enosh, Shavit; Rubin-Asher, Deborah; Lehr, Benjamin; Defrin, Ruth

    2012-02-01

    Central pain below the injury level after spinal cord injury is excruciating, chronic and resistive to treatment. Animal studies suggest that pretreatment may prevent central pain, but to date there are no measures to predict its development. Our aim was to monitor changes in the sensory profile below the lesion prior to the development of below-level central pain in order to search for a parameter that could predict its risk and to further explore its pathophysiology. Thirty patients with spinal cord injury and 27 healthy controls underwent measurement of warm, cold, heat-pain and touch thresholds as well as graphaesthesia, allodynia, hyperpathia and wind-up pain in intact region and in the shin and feet (below level). Patients were tested at 2-4 weeks, 1-2.5 months and 2.5-6 months after the injury or until central pain had developed. At the end of the follow-up, 46% of patients developed below-level central pain. During the testing periods, individuals who eventually developed central pain had higher thermal thresholds than those who did not and displayed high rates of abnormal sensations (allodynia and hyperpathia), which gradually increased with time until central pain developed. Logistic regressions revealed that the best predictor for the risk of below-level central pain was allodynia in the foot in the second testing session with a 77% probability (90.9% confidence). The results suggest that neuronal hyperexcitability, which may develop consequent to damage to spinothalamic tracts, precedes central pain. Furthermore, it appears that below-level central pain develops after a substantial build-up of hyperexcitability. To the best of our knowledge, this is the first systematic report establishing that neuronal hyperexcitability precedes central pain. Predicting the risk for central pain can be utilized to initiate early treatment in order to prevent its development.

  13. Pain inhibits pain; human brainstem mechanisms.

    Science.gov (United States)

    Youssef, A M; Macefield, V G; Henderson, L A

    2016-01-01

    Conditioned pain modulation is a powerful analgesic mechanism, occurring when a painful stimulus is inhibited by a second painful stimulus delivered at a different body location. Reduced conditioned pain modulation capacity is associated with the development of some chronic pain conditions and the effectiveness of some analgesic medications. Human lesion studies show that the circuitry responsible for conditioned pain modulation lies within the caudal brainstem, although the precise nuclei in humans remain unknown. We employed brain imaging to determine brainstem sites responsible for conditioned pain modulation in 54 healthy individuals. In all subjects, 8 noxious heat stimuli (test stimuli) were applied to the right side of the mouth and brain activity measured using functional magnetic resonance imaging. This paradigm was then repeated. However, following the fourth noxious stimulus, a separate noxious stimulus, consisting of an intramuscular injection of hypertonic saline into the leg, was delivered (conditioning stimulus). During this test and conditioning stimulus period, 23 subjects displayed conditioned pain modulation analgesia whereas 31 subjects did not. An individual's analgesic ability was not influenced by gender, pain intensity levels of the test or conditioning stimuli or by psychological variables such as pain catastrophizing or fear of pain. Brain images were processed using SPM8 and the brainstem isolated using the SUIT toolbox. Significant increases in signal intensity were determined during each test stimulus and compared between subjects that did and did not display CPM analgesia (ppain modulation circuitry provides a framework for the future investigations into the neural mechanisms responsible for the maintenance of persistent pain conditions thought to involve altered analgesic circuitry.

  14. Central hypersensitivity in chronic musculoskeletal pain.

    Science.gov (United States)

    Curatolo, Michele; Arendt-Nielsen, Lars

    2015-05-01

    Clinical research has consistently detected alteration in central pain processing leading to hypersensitivity. Most methods used in humans are reliable and have face validity to detect widespread central hypersensitivity. However, construct validity is difficult to investigate due to lack of gold standards. Reference values in the pain-free population have been generated, but need replication. Research on pain biomarkers that reflect specific central hypersensitivity processes is warranted. Few studies have analyzed the prognostic value of central hypersensitivity. Most medications acting at central level and some non-pharmacological approaches, including psychological interventions, are likely to attenuate central hypersensitivity.

  15. Central hypersensitivity in chronic musculoskeletal pain

    DEFF Research Database (Denmark)

    Curatolo, Michele; Arendt-Nielsen, Lars

    2015-01-01

    Clinical research has consistently detected alteration in central pain processing leading to hypersensitivity. Most methods used in humans are reliable and have face validity to detect widespread central hypersensitivity. However, construct validity is difficult to investigate due to lack of gold...... standards. Reference values in the pain-free population have been generated, but need replication. Research on pain biomarkers that reflect specific central hypersensitivity processes is warranted. Few studies have analyzed the prognostic value of central hypersensitivity. Most medications acting at central...... level and some non-pharmacological approaches, including psychological interventions, are likely to attenuate central hypersensitivity....

  16. Central sensitization in chronic low back pain: A narrative review.

    Science.gov (United States)

    Sanzarello, Ilaria; Merlini, Luciano; Rosa, Michele Attilio; Perrone, Mariada; Frugiuele, Jacopo; Borghi, Raffaele; Faldini, Cesare

    2016-11-21

    Low back pain is one of the four most common disorders in all regions, and the greatest contributor to disability worldwide, adding 10.7% of total years lost due to this health state. The etiology of chronic low back pain is, in most of the cases (up to 85%), unknown or nonspecific, while the specific causes (specific spinal pathology and neuropathic/radicular disorders) are uncommon. Central sensitization has been recently recognized as a potential pathophysiological mechanism underlying a group of chronic pain conditions, and may be a contributory factor for a sub-group of patients with chronic low back pain. The purposes of this narrative review are twofold. First, to describe central sensitization and its symptoms and signs in patients with chronic pain disorders in order to allow its recognition in patients with nonspecific low back pain. Second, to provide general treatment principles of chronic low back pain with particular emphasis on pharmacotherapy targeting central sensitization.

  17. Central pain processing in osteoarthritis: implications for treatment.

    Science.gov (United States)

    Hassan, Hafiz; Walsh, David A

    2014-01-01

    Osteoarthritis (OA) is a major cause of pain and is characterized by loss of articular cartilage integrity, synovitis and remodeling of subchondral bone. However, OA pain mechanisms remain incompletely understood. Pain severity does not always correlate with the extent of joint damage. Furthermore, many people with OA continue to experience pain despite optimal use of standard therapies that target the joints, including joint-replacement surgery. There is compelling evidence that altered central pain processing plays an important role in maintaining pain and increasing pain severity in some people with OA. A key challenge is to identify this subgroup of patients with abnormal central pain processing in order to improve their clinical outcomes by developing and targeting specific analgesic treatments.

  18. Differential pain modulation properties in central neuropathic pain after spinal cord injury.

    Science.gov (United States)

    Gruener, Hila; Zeilig, Gabi; Laufer, Yocheved; Blumen, Nava; Defrin, Ruth

    2016-07-01

    It seems that central neuropathic pain (CNP) is associated with altered abilities to modulate pain; whereas dysfunction in descending pain inhibition is associated with the extent of chronic pain distribution, enhanced pain excitation is associated with the intensity of chronic pain. We investigated the hypothesis that CNP is associated with decreased descending pain inhibition along with increased neuronal excitability and that both traits are associated with spinothalamic tract (STT) damage. Chronic spinal cord injury subjects with CNP (n = 27) and without CNP (n = 23) and healthy controls (n = 20) underwent the measurement of pain adaptation, conditioned pain modulation (CPM), tonic suprathreshold pain (TSP), and spatial summation of pain above injury level. Central neuropathic pain subjects also underwent at and below-lesion STT evaluation and completed the questionnaires. Central neuropathic pain subjects showed decreased CPM and increased enhancement of TSP compared with controls. Among CNP subjects, the dysfunction of CPM and pain adaptation correlated positively with the number of painful body regions. The magnitude of TSP and spatial summation of pain correlated positively with CNP intensity. STT scores correlated with CNP intensity and with TSP, so that the more affected the STT below injury level, the greater the CNP and TSP magnitude. It seems that CNP is associated with altered abilities to modulate pain, whereas dysfunction in descending pain inhibition is associated with the extent of chronic pain distribution and enhanced pain excitation is associated with the intensity of chronic pain. Thus, top-down processes may determine the spread of CNP, whereas bottom-up processes may determine CNP intensity. It also seems that the mechanisms of CNP may involve STT-induced hyperexcitability. Future, longitudinal studies may investigate the timeline of this scenario.

  19. Neuronal mechanism for neuropathic pain

    OpenAIRE

    Zhuo Min

    2007-01-01

    Abstract Among different forms of persistent pain, neuropathic pain presents as a most difficult task for basic researchers and clinicians. Despite recent rapid development of neuroscience and modern techniques related to drug discovery, effective drugs based on clear basic mechanisms are still lacking. Here, I will review the basic neuronal mechanisms that maybe involved in neuropathic pain. I will present the problem of neuropathic pain as a rather difficult task for neuroscientists, and we...

  20. Central Hyperexcitability in Chronic Musculoskeletal Pain: A Conceptual Breakthrough with Multiple Clinical Implications

    Directory of Open Access Journals (Sweden)

    Jan Lidbeck

    2002-01-01

    Full Text Available Recent investigations of dysfunctional pain processing in the central nervous system have contributed much knowledge about the development of chronic musculoskeletal pain. Many common chronic musculoskeletal pain syndromes - including regional myofascial pain syndromes, whiplash pain syndromes, refractory work-related neck-shoulder pain, certain types of chronic low back pain, fibromyalgia and others - may essentially be explained by abnormalities in central pain modulation. The growing awareness of dysfunctional central pain modulation may be a conceptual breakthrough leading to a better understanding of common chronic pain disorders. A new paradigm will have multiple clinical implications, including re-evaluation of clinical practice routines and rehabilitation methods, and will focus on controversial issues of medicolegal concern. The concept of dysfunctional central pain processing will also necessitate a mechanism-based classification of pain for the selection of individual treatment and rehabilitation programs for subgroups of patients with chronic musculoskeletal pain due to different pathophysiological mechanisms.

  1. Phantom Limb Pain: Mechanisms and Treatment Approaches

    Directory of Open Access Journals (Sweden)

    Bishnu Subedi

    2011-01-01

    Full Text Available The vast amount of research over the past decades has significantly added to our knowledge of phantom limb pain. Multiple factors including site of amputation or presence of preamputation pain have been found to have a positive correlation with the development of phantom limb pain. The paradigms of proposed mechanisms have shifted over the past years from the psychogenic theory to peripheral and central neural changes involving cortical reorganization. More recently, the role of mirror neurons in the brain has been proposed in the generation of phantom pain. A wide variety of treatment approaches have been employed, but mechanism-based specific treatment guidelines are yet to evolve. Phantom limb pain is considered a neuropathic pain, and most treatment recommendations are based on recommendations for neuropathic pain syndromes. Mirror therapy, a relatively recently proposed therapy for phantom limb pain, has mixed results in randomized controlled trials. Most successful treatment outcomes include multidisciplinary measures. This paper attempts to review and summarize recent research relative to the proposed mechanisms of and treatments for phantom limb pain.

  2. Habituation to pain: further support for a central component.

    Science.gov (United States)

    Rennefeld, C; Wiech, K; Schoell, E D; Lorenz, J; Bingel, U

    2010-03-01

    Habituation to repetitive painful stimulation may represent an important protection mechanism against the development of chronic pain states. However, the exact neurobiological mechanisms of this phenomenon remain unclear. In this study we (i) explore the somatotopic specificity of pain attenuation over time and (ii) investigate the role of the endogenous opioid system in its development. We investigated 24 healthy volunteers with a paradigm of daily painful stimulation of the left volar forearm for 1 week. Habituation was assessed by comparing pain-related responses (ratings and thresholds) between days 1 and 8. To test whether a repetition-dependent attenuation of pain is restricted to the site of stimulus application or induces additional systemic effects indicative of a central mechanism, we also measured pain-related responses at the contralateral arm and the left leg. To assess the role of the endogenous opioid system in this mechanism, we used the opioid-receptor antagonist naloxone in a double-blind design. Repetitive painful stimulation over several days resulted in a significant habituation to pain at the site of daily stimulation. In addition, we also observed significant pain attenuation at the non-stimulated limbs. This effect was less pronounced at the untreated arm compared to the treated arm and even weaker in the leg, displaying a significant Stimulation-Site x Time interaction. The development of pain habituation was unaffected by the opioid antagonist naloxone. Taken together, these results strongly support the role of central components in the mechanism of pain habituation that do not directly involve the endogenous opioid system.

  3. "BreakThrough cancer Pain" biomolecular mechanisms

    Directory of Open Access Journals (Sweden)

    Francesco Amato

    2014-11-01

    Full Text Available The BTcP is a transitory exacerbation of pain of moderate to high intensity, which occurs, either spontaneously or as a result of a trigger factor, in patients with pain basic maintained for most of the day or under control of mild . The pathophysiological mechanisms underlying the development and maintenance of this type of pain seem to depend on several factors including an increase in the activity of the receptors TRPV1, central sensitization, activation of Glia etc. To better manage the disease can interfere with rapid analgesia of short duration that best overlaps the temporal characteristics of BTcP.

  4. Neuropathic pain due to malignancy: Mechanisms, clinical manifestations and therapy

    Directory of Open Access Journals (Sweden)

    Pjević Miroslava

    2004-01-01

    Full Text Available Introduction Neuropathic pain in cancer patients requires a focused clinical evaluation based on knowledge of common neuropathic pain syndromes. Definition Neuropathic pain is a non-nociceptive pain or "differentiation" pain, which suggests abnormal production of impulses by neural tissue that is separated from afferent input. Impulses arise from the peripheral nervous system or central nervous system. Causes of neuropathic pain due to malignancy Neuropathic pain is caused directly by cancer-related pathology (compression/infiltration of nerve tissue, combination of compression/infiltration or by diagnostic and therapeutic procedures (surgical procedures, chemotherapy, radiotherapy. Mechanisms Pathophysiological mechanisms are very complex and still not clear enough. Neuropathic pain is generated by electrical hyperactivity of neurons along the pain pathways. Peripheral mechanisms (primary sensitization of nerve endings, ectopically generated action potentials within damaged nerves, abnormal electrogenesis within sensory ganglia and central mechanisms (loss of input from peripheral nociceptors into dorsal horn, aberrant sprouting within dorsal horn, central sensitization, loss of inhibitory interneurons, mechanisms at higher centers are involved. Diagnosis The quality of pain presents as spontaneous pain (continuous and paroxysmal, abnormal pain (allodynia, hyperalgesia, hyperpathia, paroxysmal pain. Clinical manifestations Clinically, neuropathic pain is described as the pain in the peripheral nerve (cranial nerves, other mononeuropathies, radiculopathy, plexopathy, paraneoplastic peripheral neuropathy and relatively infrequent, central pain syndrome. Therapy Treatment of neuropathic pain remains a challenge for clinicians, because there is no accepted algorithm for analgesic treatment of neuropathic pain. Pharmacotherapy is considered to be the first line therapy. Opioids combined with non-steroidal antiinflammatory drugs are warrented. If

  5. A Review of Select Centralized Pain Syndromes

    Directory of Open Access Journals (Sweden)

    David R. Spiegel

    2015-01-01

    Full Text Available Pain can be broadly divided into 3 classes, including nociceptive or inflammatory pain (protective, neuropathic (pathological, occurring after damage to the nervous system, or centralized (pathological, due to abnormal function but with no damage or inflammation to the nervous system. The latter has been posited to occur when descending analgesic pathways are attenuated and/or glutamatergic transmission is facilitated. Additionally, this “pain prone phenotype” can be associated with early life trauma and a suboptimal response to opiates. This article will review the relationships between centralized pain syndromes (ie, fibromyalgia, chronic low back pain, childhood sexual abuse, and opiate misuse. Finally, treatment implications, potentially effecting primary care physicians, will be discussed.

  6. Sad mood increases pain sensitivity upon thermal grill illusion stimulation: implications for central pain processing.

    Science.gov (United States)

    Boettger, Michael Karl; Schwier, Christiane; Bär, Karl-Jürgen

    2011-01-01

    In different fields of neuroscience research, illusions have successfully been used to unravel underlying mechanisms of stimulus processing. One such illusion existing for the field of pain research is the so-called thermal grill illusion. Here, painful sensations are elicited by interlacing warm and cold bars, with stimulus intensities (temperatures) of these bars being below the respective heat pain or cold pain thresholds. To date, the underlying mechanisms of this phenomenon are not completely understood. There is some agreement, however, that the sensation evoked by this stimulation is generated by central nervous interactions. Therefore, we followed two approaches in this study: firstly, we aimed at developing and validating a water-driven device which might be used in fMRI scanners in future studies - subject to minor adaptations. Secondly, we aimed to interfere with this illusion by induction of a sad mood state, a procedure which is suggested to influence central nervous structures that are also involved in pain processing. The newly developed device induced thermal grill sensations similar to those reported in the literature. Induction of sad, but not neutral mood states, resulted in higher pain and unpleasantness ratings of the painful illusion. These findings might be of importance for the understanding of pain processing in healthy volunteers, but putatively even more so in patients with major depressive disorder. Moreover, our results might indicate that central nervous structures involved in the affective domain or cognitive domain of pain processing might be involved in the perception of the illusion.

  7. Central representation of muscle pain and mechanical hyperesthesia in the orofacial region: a positron emission tomography study

    DEFF Research Database (Denmark)

    Kupers, Rron; Svensson, Peter; Jensen, Troels Staehlin

    2004-01-01

    Functional neuroimaging studies of the human brain have revealed a network of brain regions involved in the processing of nociceptive information. However, little is known of the cerebral processing of pain originating from muscles. The aim of this study was to investigate the cerebral activation...

  8. Recognition of central sensitization in patients with musculoskeletal pain: Application of pain neurophysiology in manual therapy practice.

    NARCIS (Netherlands)

    Nijs, J.; Houdenhove, B. Van; Oostendorp, R.A.B.

    2010-01-01

    Central sensitization plays an important role in the pathophysiology of numerous musculoskeletal pain disorders, yet it remains unclear how manual therapists can recognize this condition. Therefore, mechanism based clinical guidelines for the recognition of central sensitization in patients with mus

  9. Clinical analysis and treatment of central pain due to headinjury

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@Central pain is induced by the involvement of the abnormal pain pathway due to diseases of the central nervous system. Central pain after brain trauma is common clinically, but it is often misdiagnosed and neglected because of lack of objective disturbances. We treated 20 cases of central pain after head injury by invigorating blood circulation and satisfactory result was obtained.

  10. Facilitated pro-nociceptive pain mechanisms in radiating back pain compared with localized back pain

    DEFF Research Database (Denmark)

    Vaegter, Henrik Bjarke; Palsson, Thorvaldur Skuli; Graven-Nielsen, Thomas

    2017-01-01

    Facilitated pain mechanisms and impaired pain inhibition are often found in chronic pain patients. This study compared clinical pain profiles, pain sensitivity, as well as pro-nociceptive and anti-nociceptive mechanisms in patients with localized low back pain (n=18), localized neck pain (n=17......), low back and radiating leg pain (n=18), or neck and radiating arm pain (n=17). It was hypothesized that patients with radiating pain had facilitated pain mechanisms and impaired pain inhibition compared with localized pain patients. Cuff algometry was performed on the non-painful lower leg to assess...... pressure pain threshold (cPPT), tolerance (cPTT), temporal summation of pain (TSP: increase in pain scores to ten repeated stimulations at cPTT intensity), and conditioning pain modulation (CPM: increase in cPPT during cuff pain conditioning on the contralateral leg). Heat detection (HDT) and heat pain...

  11. Correlation between altered central pain processing and concentration of peritoneal fluid inflammatory cytokines in endometriosis patients with chronic pelvic pain.

    Science.gov (United States)

    Neziri, Alban Y; Bersinger, Nick A; Andersen, Ole K; Arendt-Nielsen, Lars; Mueller, Michael D; Curatolo, Michele

    2014-01-01

    Translational research has not yet elucidated whether alterations in central pain processes are related to peripheral inflammatory processes in chronic pain patients. We tested the hypothesis that the concentration of cytokines in the peritoneal fluid of endometriosis patients with chronic pain correlate with parameters of hyperexcitability of the nociceptive system. The concentrations of 15 peritoneal fluid cytokines were measured in 11 patients with chronic pelvic pain and a diagnosis of endometriosis. Six parameters assessing central pain processes were recorded. Positive correlations between concentration of some cytokines in the peritoneal fluid and amplification of central pain processing were found. The results suggest that inflammatory mechanisms may be important in the pathophysiology of altered central pain processes and that cytokines produced in the environment of endometriosis could act as mediators between the peripheral lesion and changes in central nociceptive processes.

  12. Pain pathoetiology after TBI: neural and nonneural mechanisms.

    Science.gov (United States)

    Walker, William C

    2004-01-01

    Individuals recovering from traumatic brain injury (TBI) frequently experience acute and chronic pain. Their pain experience is the net effect of many interacting and very complex physiologic, biochemical, and psychological mechanisms involving both the peripheral and central nervous system. This article reviews the basics of neural mechanisms and pathways of pain after TBI, and discusses clinical implications. Numerous intracranial and extracranial tissues must be considered in the evaluation of pain after TBI, with the specific mechanism of trauma influencing the anatomic distribution of injuries. The differential diagnosis usually falls into one of the following pathoetiologic classifications: primary or secondary musculoskeletal, vascular, visceral, and neural pain syndromes.

  13. Central pain: definition, phisiopathology and therapy

    Directory of Open Access Journals (Sweden)

    Vincenzo Moschini

    2012-12-01

    Full Text Available Central pain is the expression of an injury and/or a primary or secondary dysfunction of the central nervous system.1 It is based on total or partial damage along the spinal-thalamic-cortical pathways and it may have cerebral or spinal origin. It has variable incidence according to its etiology: 8-10% in stroke patients, 30% in multiple sclerosis patients, 30-60% in paraplegic patients.2-3 At the spinal level, the most frequent causes are: traumatic injuries, cancer, plaques from multiple sclerosis, syringomyelia. In this review, we examine the main symptoms that contribute to confirm the diagnosis of central pain, neuropathic or thalamic. The presence of nerve injury, evaluated by neuroimaging and neurophysiological tests, allows us to complete the diagnostic picture.

  14. The role of the central nervous system in osteoarthritis pain and implications for rehabilitation.

    Science.gov (United States)

    Murphy, Susan L; Phillips, Kristine; Williams, David A; Clauw, Daniel J

    2012-12-01

    It has been known for some time that central nervous system (CNS) pain amplification is present in some individuals with osteoarthritis; the implications of this involvement, however, are just starting to be realized. In the past year, several research reviews have focused on evidence supporting shared mechanisms across chronic pain conditions for how pain is generated and maintained in the CNS, irrespective of the underlying structural pathology. This review article focuses on current literature describing CNS amplification in osteoarthritis by discussing peripheral sensitization, central sensitization, and central augmentation, and the clinical manifestation of central augmentation referred to as centralized pain, and offers considerations for rehabilitation treatment and future directions for research.

  15. Central poststroke pain: somatosensory abnormalities and the presence of associated myofascial pain syndrome

    Directory of Open Access Journals (Sweden)

    de Oliveira Rogério Adas

    2012-09-01

    Full Text Available Abstract Background Central post-stroke pain (CPSP is a neuropathic pain syndrome associated with somatosensory abnormalities due to central nervous system lesion following a cerebrovascular insult. Post-stroke pain (PSP refers to a broader range of clinical conditions leading to pain after stroke, but not restricted to CPSP, including other types of pain such as myofascial pain syndrome (MPS, painful shoulder, lumbar and dorsal pain, complex regional pain syndrome, and spasticity-related pain. Despite its recognition as part of the general PSP diagnostic possibilities, the prevalence of MPS has never been characterized in patients with CPSP patients. We performed a cross-sectional standardized clinical and radiological evaluation of patients with definite CPSP in order to assess the presence of other non-neuropathic pain syndromes, and in particular, the role of myofascial pain syndrome in these patients. Methods CPSP patients underwent a standardized sensory and motor neurological evaluation, and were classified according to stroke mechanism, neurological deficits, presence and profile of MPS. The Visual Analogic Scale (VAS, McGill Pain Questionnaire (MPQ, and Beck Depression Scale (BDS were filled out by all participants. Results Forty CPSP patients were included. Thirty-six (90.0% had one single ischemic stroke. Pain presented during the first three months after stroke in 75.0%. Median pain intensity was 10 (5 to 10. There was no difference in pain intensity among the different lesion site groups. Neuropathic pain was continuous-ongoing in 34 (85.0% patients and intermittent in the remainder. Burning was the most common descriptor (70%. Main aggravating factors were contact to cold (62.5%. Thermo-sensory abnormalities were universal. MPS was diagnosed in 27 (67.5% patients and was more common in the supratentorial extra-thalamic group (P Conclusions The presence of MPS is not an exception after stroke and may present in association with CPSP

  16. Unraveling the central processing of pain by studying brain activity and behaviour in rats

    NARCIS (Netherlands)

    Schaap, M.W.H.

    2013-01-01

    Pain is described as a subjective unpleasant sensory and emotional experience, which is generated in the brain. In both humans and animals, pain is frequently undertreated. The primary barrier to an effective pain treatment is the incomplete knowledge about underlying central mechanisms. In animals,

  17. Nociceptive transmission and modulation via P2X receptors in central pain syndrome.

    Science.gov (United States)

    Kuan, Yung-Hui; Shyu, Bai-Chuang

    2016-05-26

    Painful sensations are some of the most frequent complaints of patients who are admitted to local medical clinics. Persistent pain varies according to its causes, often resulting from local tissue damage or inflammation. Central somatosensory pathway lesions that are not adequately relieved can consequently cause central pain syndrome or central neuropathic pain. Research on the molecular mechanisms that underlie this pathogenesis is important for treating such pain. To date, evidence suggests the involvement of ion channels, including adenosine triphosphate (ATP)-gated cation channel P2X receptors, in central nervous system pain transmission and persistent modulation upon and following the occurrence of neuropathic pain. Several P2X receptor subtypes, including P2X2, P2X3, P2X4, and P2X7, have been shown to play diverse roles in the pathogenesis of central pain including the mediation of fast transmission in the peripheral nervous system and modulation of neuronal activity in the central nervous system. This review article highlights the role of the P2X family of ATP receptors in the pathogenesis of central neuropathic pain and pain transmission. We discuss basic research that may be translated to clinical application, suggesting that P2X receptors may be treatment targets for central pain syndrome.

  18. MECHANISMS OF CHRONIC PAIN AT OSTEOARTHROSIS OF THE KNEE

    Directory of Open Access Journals (Sweden)

    E. F. Turovskaya

    2014-01-01

    Full Text Available The main symptom of osteoarthritis (OA is pain. Mechanisms of chronic pain in OA have not been fully investigated yet.Objective: to study key mechanisms of chronic pain in patients with knee OA.Subjects and methods. Authors examined 80 women aged 45–65 years, with chronic pain due to OA of the knee. Clinical rheumatologic and neurologic examinations, screening for neuropathic pain (PainDETECT and DN4 questionnaires, estimation of duration and intensity of pain, WOMAC assessment and evaluation of affective disorders (HADS questionnaire were performed. X-ray and ultrasonography were used to assess destructive changes of theknee.Results. According to DN4 questionnaire, 25 (30% patients scored 4 and more, i. e. had signs of neuropathic pain, whereas 55 (70% did not (scored less than 4. Although neurologic examination did not reveal lesions of somatosensory system in neither of groups, assessment of the pain sensitivity showed hyperalgesia in 60% of cases. Patients with signs of neuropathic pain typically have secondary hyperalgesia propagating far from the damaged joint.Conclusion. 30% of patients with osteoarthritis have pain of different intensity determined by nociceptive and neuropathic mechanisms. At the same time the absence of lesions of somatosensory system does not let us to consider the pain neuropathic and indicates that it has dysfunctional nature. Signs of neuropathic pain associated with secondary hyperalgesia may be a clinical symptom of central sensitization. Due to this fact, reasonable therapy of osteoarthritis-associated chronic pain should include, besides NSAIDs, central acting drugs for neuropathic pain treatment.

  19. Neuroimmunological mechanisms of chronic pain syndrome

    Directory of Open Access Journals (Sweden)

    I. A. Vyshlova

    2016-01-01

    Full Text Available The article considers the mechanisms of chronic low back pain. Three pathophysiological mechanisms: nociceptive, neurogenic (neuropathic, and psychogenic are noted to be involved in the development of pain syndrome. The role of cellular and molecular changes in the posterior horn and in the somatosensory dysregulated mechanism of neuropathic pain is shown. Immunological processes, including neurohumoral (serotoninergic and hormonal (sex hormones and specific proteins ones, play an important role in the development of pain. The generalization and further study of these mechanisms are embodied in approaches to therapy for pain syndromes and hence these require analysis and further investigation. 

  20. Craniofacial muscle pain: review of mechanisms and clinical manifestations.

    Science.gov (United States)

    Svensson, P; Graven-Nielsen, T

    2001-01-01

    Epidemiologic surveys of temporomandibular disorders (TMD) have demonstrated that a considerable proportion of the population--up to 5% or 6%--will experience persistent pain severe enough to seek treatment. Unfortunately, the current diagnostic classification of craniofacial muscle pain is based on descriptions of signs and symptoms rather than on knowledge of pain mechanisms. Furthermore, the pathophysiology and etiology of craniofacial muscle pain are not known in sufficient detail to allow causal treatment. Many hypotheses have been proposed to explain cause-effect relationships; however, it is still uncertain what may be the cause of muscle pain and what is the effect of muscle pain. This article reviews the literature in which craniofacial muscle pain has been induced by experimental techniques in animals and human volunteers and in which the effects on somatosensory and motor function have been assessed under standardized conditions. This information is compared to the clinical correlates, which can be derived from the numerous cross-sectional studies in patients with craniofacial muscle pain. The experimental literature clearly indicates that muscle pain has significant effects on both somatosensory and craniofacial motor function. Typical somatosensory manifestations of experimental muscle pain are referred pain and increased sensitivity of homotopic areas. The craniofacial motor function is inhibited mainly during experimental muscle pain, but phase-dependent excitation is also found during mastication to reduce the amplitude and velocity of jaw movements. The underlying neurobiologic mechanisms probably involve varying combinations of sensitization of peripheral afferents, hyperexcitability of central neurons, and imbalance in descending pain modulatory systems. Reflex circuits in the brain stem seem important for the adjustment of sensorimotor function in the presence of craniofacial pain. Changes in somatosensory and motor function may therefore be

  1. Central sensitization: implications for the diagnosis and treatment of pain.

    Science.gov (United States)

    Woolf, Clifford J

    2011-03-01

    Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the

  2. [Neuronal mechanisms underlying pain-induced negative emotions].

    Science.gov (United States)

    Minami, Masabumi

    2012-11-01

    Pain consists of sensory-discriminative and negative emotional components. Although the neuronal basis of the sensory component of pain has been studied extensively, the neuronal mechanisms underlying the negative emotional component are not well understood. Recently, behavioral studies using a conditioned place paradigm have successfully elucidated the neuronal circuits and mechanisms underlying the negative emotional component of pain. Excitotoxic lesions of the anterior cingulate cortex (ACC), central amygdaloid nucleus, basolateral amygdaloid nucleus (BLA), or bed nucleus of the stria terminalis (BNST) suppress intraplantar formalin-induced aversive responses. Glutamatergic transmission within the ACC and BLA via N-methyl-D-asparate (NMDA) receptors has been shown to play a critical role in these aversive responses. In the BNST, especially its ventral part, noradrenergic transmission via β-adrenergic receptors has been shown to be important for pain-induced aversion. Because persistent pain is frequently associated with psychological and emotional dysfunctions, studies on the neuronal circuits and molecular mechanisms involved in the negative emotional component of pain may have considerable clinical importance in the treatment of chronic pain. Here, I have reviewed behavioral studies investigating the neuronal mechanisms underlying the negative emotional component of pain and have introduced our data showing the pivotal role of amygdala and BNST in pain-induced aversion.

  3. Mechanism of Chronic Pain in Rodent Brain Imaging

    Science.gov (United States)

    Chang, Pei-Ching

    Chronic pain is a significant health problem that greatly impacts the quality of life of individuals and imparts high costs to society. Despite intense research effort in understanding of the mechanism of pain, chronic pain remains a clinical problem that has few effective therapies. The advent of human brain imaging research in recent years has changed the way that chronic pain is viewed. To further extend the use of human brain imaging techniques for better therapies, the adoption of imaging technique onto the animal pain models is essential, in which underlying brain mechanisms can be systematically studied using various combination of imaging and invasive techniques. The general goal of this thesis is to addresses how brain develops and maintains chronic pain in an animal model using fMRI. We demonstrate that nucleus accumbens, the central component of mesolimbic circuitry, is essential in development of chronic pain. To advance our imaging technique, we develop an innovative methodology to carry out fMRI in awake, conscious rat. Using this cutting-edge technique, we show that allodynia is assoicated with shift brain response toward neural circuits associated nucleus accumbens and prefrontal cortex that regulate affective and cognitive component of pain. Taken together, this thesis provides a deeper understanding of how brain mediates pain. It builds on the existing body of knowledge through maximizing the depth of insight into brain imaging of chronic pain.

  4. Mechanisms of pain from urinary tract infection.

    Science.gov (United States)

    Rosen, John M; Klumpp, David J

    2014-04-01

    The pain response to urinary tract infection is largely uncharacterized, but the symptomatic response to urinary tract infection contrasts with the lack of pain response among individuals with asymptomatic bacteriuria. Quantifying pelvic pain in a murine urinary tract infection model, uropathogenic Escerichia coli induces transient pelvic pain, whereas an asymptomatic bacteriuria E. coli isolate causes no pain, thus recapitulating the spectrum of clinical responses to intravesical E. coli. These differential pain responses are not correlated with bladder colonization or inflammation, but instead are intrinsic to E. coli lipopolysaccharide and dependent on the lipopolysaccharide receptor, TLR4. Epidemiological data suggest a link between interstitial cystitis and a history of urinary tract infection, so it was evaluated whether repetitive uropathogenic E. coli instillation would result in chronic pain through central sensitization. Although repeated infection with wild type uropathogenic E. coli results in only transient episodes of acute pain, a uropathogenic E. coli mutant lacking O-antigen causes chronic, post-urinary tract infection pelvic pain. Similarly, a K-12 E. coli strain lacking O-antigen induces chronic pain that persisted long after bacterial clearance, and expressing O-antigen nullified the pain phenotype. Spinal cords isolated from mice with post-urinary tract infection chronic pain showed deficits in short-term depression consistent with central sensitization. Deleting O-antigen gene complex from a uropathogenic E. coli strain and subsequent heterologous expression of O-antigen gene clusters shows that a single bacterial isolate can exhibit pain phenotypes ranging from a null phenotype, an acute pain phenotype, to a chronic pain phenotype. Post-urinary tract infection chronic pain is also associated with voiding dysfunction and anxious/depressive behavior. These effects are also mediated by TRPV1 at the level of pain establishment

  5. Myofascial Pain: Mechanisms to Management.

    Science.gov (United States)

    Fricton, James

    2016-08-01

    More than 100 million adults in the United States have chronic pain conditions, costing more than $500 billion annually in medical care and lost productivity. They are the most common reason for seeking health care, for disability and addiction, and the highest driver of health care costs. Myofascial pain is the most common condition causing chronic pain and can be diagnosed through identifying clinical characteristics and muscle palpation. Management is focused on integrating patient training in changing lifestyle risk factors with evidence-based treatment. Understanding the cause, diagnosis, and management of myopain conditions will help prevent the impact of chronic pain.

  6. Neural mechanisms of pain: an overview.

    Science.gov (United States)

    Casey, K L

    1982-01-01

    There are two essential components of pain: discriminative and affective. The discriminative component includes the ability to identify the stimulus as originating from somatic or visceral tissue, determine some of the physical properties of the stimulus, and localize it in space, time, and along a continuum of intensities. The affective component is the experience of aversiveness which motivates escape, avoidance, and protective behavior. Both of these components of pain were acknowledged by Sir Charles Sherrington (1947) and must be considered in any discussion of the neurophysiological basis of pain. The neural mechanisms subserving discrimination and affect are different and may be differentially affected by drugs or surgical procedures. A consideration of pain mechanisms must also include the neural systems modulating pain, for it is well known that pain can be profoundly influenced by other somatic stimuli and by attentional, emotional, and cognitive factors. A thorough and detailed discussion of pain mechanisms is beyond the scope of this brief overview, but I will cover major features of the neural mechanisms currently thought to underlie the discriminative and affective dimensions of pain and the mechanisms by which pain may be modulated.

  7. Imaging in mechanical back pain

    DEFF Research Database (Denmark)

    Hansen, Bjarke Brandt; Hansen, Philip; Carrino, John A;

    2016-01-01

    Low back pain is common and relates to a variety of overlapping pathologies. Within the last few decades, almost every medical imaging modality has been applied in the evaluation of low back pain. Imaging of the spine has a high priority in the assessment of patients with low back pain, who seem...... and symptoms hampers the ability of clinicians to devise a specific treatment plan for the patient. Therefore, there is mounting interest in new imaging techniques of the lumbar spine that may increase the clinical correlation in low back pain. In this review, we will discuss the value and limitations...... to expect such procedures to be undertaken. However, the majority of conventional imaging techniques do not have adequate precision to identify the primary source of pain. Not only can this be frustrating to both clinicians and patients, but importantly, inadequate correlation between imaging findings...

  8. Psychophysical and cerebral responses to heat stimulation in patients with central pain, painless central sensory loss, and in healthy persons.

    Science.gov (United States)

    Casey, Kenneth L; Geisser, Michael; Lorenz, Jürgen; Morrow, Thomas J; Paulson, Pamela; Minoshima, Satoshi

    2012-02-01

    Patients with central pain (CP) typically have chronic pain within an area of reduced pain and temperature sensation, suggesting an impairment of endogenous pain modulation mechanisms. We tested the hypothesis that some brain structures normally activated by cutaneous heat stimulation would be hyperresponsive among patients with CP but not among patients with a central nervous system lesion causing a loss of heat or nociceptive sensation with no pain (NP). We used H(2)(15)O positron emission tomography to measure, in 15 healthy control participants, 10 NP patients, and 10 CP patients, increases in regional cerebral blood flow among volumes of interest (VOI) from the resting (no stimulus) condition during bilateral contact heat stimulation at heat detection, heat pain threshold, and heat pain tolerance levels. Both patient groups had a reduced perception of heat intensity and unpleasantness on the clinically affected side and a bilateral impairment of heat detection. Compared with the HC group, both NP and CP patients had more hyperactive and hypoactive VOI in the resting state and more hyperresponsive and hyporesponsive VOI during heat stimulation. Compared with NP patients, CP patients had more hyperresponsive VOI in the intralaminar thalamus and sensory-motor cortex during heat stimulation. Our results show that focal CNS lesions produce bilateral sensory deficits and widespread changes in the nociceptive excitability of the brain. The increased nociceptive excitability within the intralaminar thalamus and sensory-motor cortex of our sample of CP patients suggests an underlying pathophysiology for the pain in some central pain syndromes.

  9. Mechanism for chronic pain generation

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Neuropathic pain and the other abnormalities of sensation induced by axon injury or by peripheral nerve inflammation should result from functional compensations of the injured neurons during their regeneration. Ectopic distribution of proteins related to Na+, K+ and Ca2+ channels as well as of receptors on both membranes of injured axon and its cell body becomes a main pacemaker from which spontaneous ectopic afferent of primary sensatory neurons and crosstalk between neurons occur. Abnormal ectopic afferent activities lead to disorders of the sensation, such as hyperalgesia, allodynia, spontaneous pain and paraesthesia. Administration of some ion channel agents and/or α2-adrenergic blockers has shown efficiency in preventing neuropathic pain development and in relieving neuropathic pain.

  10. Effect of intravenous tropisetron on modulation of pain and central hypersensitivity in chronic low back pain patients.

    Science.gov (United States)

    Neziri, Alban Y; Dickenmann, Martina; Scaramozzino, Pasquale; Andersen, Ole K; Arendt-Nielsen, Lars; Dickenson, Anthony H; Curatolo, Michele

    2012-02-01

    The activation of 5-hydroxytryptamine-3 (5-HT-3) receptors in spinal cord can enhance intrinsic spinal mechanisms of central hypersensitivity, possibly leading to exaggerated pain responses. Clinical studies suggest that 5-HT-3 receptor antagonists may have an analgesic effect. This randomized, double-blind, placebo-controlled crossover study tested the hypothesis that the 5-HT-3 receptor antagonist tropisetron attenuates pain and central hypersensitivity in patients with chronic low back pain. Thirty patients with chronic low back pain, 15 of whom were women (aged 53 ± 14 years) and 15 men (aged 48 ± 14 years), were studied. A single intravenous injection of 0.9% saline solution, tropisetron 2mg, and tropisetron 5mg was administrated in 3 different sessions, in a double-blind crossover manner. The main outcome was the visual analogue scale (VAS) score of spontaneous low back pain before, and 15, 30, 60, and 90 minutes after drug administration. Secondary outcomes were nociceptive withdrawal reflexes to single and repeated electrical stimulation, area of reflex receptive fields, pressure pain detection and tolerance thresholds, conditioned pain modulation, and area of clinical pain. The data were analyzed by analysis of variance and panel multiple regressions. All 3 treatments reduced VAS scores. However, there was no statistically significant difference between tropisetron and placebo in VAS scores. Compared to placebo, tropisetron produced a statistically significant increase in pain threshold after single electrical stimulation, but no difference in all other secondary outcomes was found. A single-dose intravenous administration of tropisetron in patients with chronic low back pain had no significant specific effect on intensity of pain and most parameters of central hypersensitivity.

  11. Common mechanisms of pain and depression: Are antidepressants also analgesics?

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    Tereza eNekovarova

    2014-03-01

    Full Text Available Neither pain, nor depression exist as independent phenomena per se, they are highly subjective inner states, formed by our brain and built on the bases of our experiences, cognition and emotions. Chronic pain is associated with changes in brain physiology and anatomy. It has been suggested that the neuronal activity underlying subjective perception of chronic pain may be divergent from the activity associated with acute pain. We will discuss the possible common pathophysiological mechanism of chronic pain and depression with respect to the default mode network of the brain, neuroplasticity and the effect of antidepressants on these two pathological conditions. The default mode network of the brain has an important role in the representation of introspective mental activities and therefore can be considered as a nodal point, common for both chronic pain and depression. Neuroplasticity which involves molecular, cellular and synaptic processes modifying connectivity between neurons and neuronal circuits can also be affected by pathological states such as chronic pain or depression. We suppose that pathogenesis of depression and chronic pain shares common negative neuroplastic changes in the central nervous system. The positive impact of antidepressants would result in a reduction of these pathological cellular/molecular processes and in the amelioration of symptoms, but it may also increase survival times and quality of life of patients with chronic cancer pain.

  12. Central Pain Following Cord Severance for Cephalosomatic Anastomosis.

    Science.gov (United States)

    Canavero, Sergio; Bonicalzi, Vincenzo

    2016-04-01

    One of the key obstacles to a successful head transplant is the possible onset of central pain, a chronic pain condition that would impair the quality of life of the transplantee. In this review, we provide the reader with a knowledge of this neglected aspect of the head transplant initiative and outline the management should this eventuality occur.

  13. Acupuncture for Visceral Pain: Neural Substrates and Potential Mechanisms

    Directory of Open Access Journals (Sweden)

    Shuping Chen

    2014-01-01

    Full Text Available Visceral pain is the most common form of pain caused by varied diseases and a major reason for patients to seek medical consultation. Despite much advances, the pathophysiological mechanism is still poorly understood comparing with its somatic counterpart and, as a result, the therapeutic efficacy is usually unsatisfactory. Acupuncture has long been used for the management of numerous disorders in particular pain and visceral pain, characterized by the high therapeutic benefits and low adverse effects. Previous findings suggest that acupuncture depresses pain via activation of a number of neurotransmitters or modulators including opioid peptides, serotonin, norepinephrine, and adenosine centrally and peripherally. It endows us, by advancing the understanding of the role of ion channels and gut microbiota in pain process, with novel perspectives to probe the mechanisms underlying acupuncture analgesia. In this review, after describing the visceral innervation and the relevant afferent pathways, in particular the ion channels in visceral nociception, we propose three principal mechanisms responsible for acupuncture induced benefits on visceral pain. Finally, potential topics are highlighted regarding the future studies in this field.

  14. Peripheral and Central Neuroinflammatory Changes and Pain Behaviors in an Animal Model of Multiple Sclerosis.

    Science.gov (United States)

    Duffy, Samuel S; Perera, Chamini J; Makker, Preet G S; Lees, Justin G; Carrive, Pascal; Moalem-Taylor, Gila

    2016-01-01

    Pain is a widespread and debilitating symptom of multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system. Although central neuroinflammation and demyelination have been implicated in MS-related pain, the contribution of peripheral and central mechanisms during different phases of the disease remains unclear. In this study, we used the animal model experimental autoimmune encephalomyelitis (EAE) to examine both stimulus-evoked and spontaneous pain behaviors, and neuroinflammatory changes, over the course of chronic disease. We found that mechanical allodynia of the hind paw preceded the onset of clinical EAE but was unmeasurable at clinical peak. This mechanical hypersensitivity coincided with increased microglial activation confined to the dorsal horn of the spinal cord. The development of facial mechanical allodynia also emerged in preclinical EAE, persisted at the clinical peak, and corresponded with pathology of the peripheral trigeminal afferent pathway. This included T cell infiltration, which arose prior to overt central lesion formation and specific damage to myelinated neurons during the clinical peak. Measurement of spontaneous pain using the mouse grimace scale, a facial expression-based coding system, showed increased facial grimacing in mice with EAE during clinical disease. This was associated with multiple peripheral and central neuroinflammatory changes including a decrease in myelinating oligodendrocytes, increased T cell infiltration, and macrophage/microglia and astrocyte activation. Overall, these findings suggest that different pathological mechanisms may underlie stimulus-evoked and spontaneous pain in EAE, and that these behaviors predominate in unique stages of the disease.

  15. Peripheral and central neuroinflammatory changes and pain behaviours in an animal model of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Samuel Shaw Duffy

    2016-09-01

    Full Text Available Pain is a widespread and debilitating symptom of multiple sclerosis (MS, a chronic inflammatory demyelinating disease of the central nervous system. Although central neuroinflammation and demyelination have been implicated in MS-related pain, the contribution of peripheral and central mechanisms during different phases of the disease remains unclear. In this study, we used the animal model experimental autoimmune encephalomyelitis (EAE to examine both stimulus-evoked and spontaneous pain behaviours, and neuroinflammatory changes, over the course of chronic disease. We found that mechanical allodynia of the hind paw preceded the onset of clinical EAE, but was unmeasurable at clinical peak. This mechanical hypersensitivity coincided with increased microglial activation confined to the dorsal horn of the spinal cord. The development of facial mechanical allodynia also emerged in pre-clinical EAE, persisted at the clinical peak, and corresponded with pathology of the peripheral trigeminal afferent pathway. This included T cell infiltration, which arose prior to overt central lesion formation, and specific damage to myelinated neurons during the clinical peak. Measurement of spontaneous pain using the mouse grimace scale, a facial expression-based coding system, showed increased facial grimacing in mice with EAE during clinical disease. This was associated with multiple peripheral and central neuroinflammatory changes including a decrease in myelinating oligodendrocytes, increased T cell infiltration and macrophage/microglia and astrocyte activation. Overall, these findings suggest that different pathological mechanisms may underlie stimulus-evoked and spontaneous pain in EAE, and that these behaviours predominate in unique stages of the disease.

  16. Correlation of Mechanical Factors and Gallbladder Pain

    Directory of Open Access Journals (Sweden)

    W. G. Li

    2008-01-01

    Full Text Available Acalculous biliary pain occurs in patients with no gallstones, but is similar to that experienced by patients with gallstones. Surgical removal of the gallbladder (GB in these patients is only successful in providing relief of symptoms to about half of those operated on, so a reliable pain-prediction model is needed. In this paper, a mechanical model is developed for the human biliary system during the emptying phase, based on a clinical test in which GB volume changes are measured in response to a standard stimulus and a recorded pain profile. The model can describe the bile emptying behaviour, the flow resistance in the biliary ducts, the peak total stress, including the passive and active stresses experienced by the GB during emptying. This model is used to explore the potential link between GB pain and mechanical factors. It is found that the peak total normal stress may be used as an effective pain indicator for GB pain. When this model is applied to clinical data of volume changes due to Cholecystokinin stimulation and pain from 37 patients, it shows a promising success rate of 88.2% in positive pain prediction.

  17. Evidence for a central mode of action for etoricoxib (COX-2 inhibitor) in patients with painful knee osteoarthritis.

    Science.gov (United States)

    Arendt-Nielsen, Lars; Egsgaard, Line Lindhardt; Petersen, Kristian Kjær

    2016-08-01

    The COX-2 inhibitor etoricoxib modulates the peripheral and central nociceptive mechanisms in animals. This interaction has not been studied in patients with pain. This randomized, double-blind, placebo-controlled, 2-way crossover, 4-week treatment study investigated the pain mechanisms modulated by etoricoxib in patients with painful knee osteoarthritis. Patients were randomized to group A (60 mg/d etoricoxib followed by placebo) or B (placebo followed by 60 mg/d etoricoxib). The quantitative, mechanistic pain biomarkers were pressure pain thresholds, temporal summation (TS), and conditioning pain modulation. Clinical readouts were Brief Pain Inventory, WOMAC, painDETECT questionnaire (PD-Q), and time and pain intensity during walking and stair climbing. Etoricoxib as compared with placebo significantly modulated the pressure pain thresholds (P = 0.012, localized sensitization) at the knee and leg (control site) (P = 0.025, spreading sensitization) and TS assessed from the knee (P = 0.038) and leg (P = 0.045). Conditioning pain modulation was not modulated. The Brief Pain Inventory (pain scores), PD-Q, WOMAC, and walking and stair climbing tests were all significantly improved by etoricoxib. Based on a minimum of 30% or 50% pain alleviation (day 0-day 28), responders and nonresponders were defined. The nonresponders showed a significant association between increased facilitation of TS and increased pain alleviation. None of the other parameters predicted the degree of pain alleviation. Generally, a responder to etoricoxib has the most facilitated TS. In conclusion, etoricoxib (1) modulated central pain modulatory mechanisms and (2) improved pain and function in painful osteoarthritis. Stronger facilitation of TS may indicate a better response to etoricoxib, supporting the central mode-of-action of the drug.

  18. Central Pain Processing in Early-Stage Parkinson's Disease: A Laser Pain fMRI Study

    Science.gov (United States)

    Petschow, Christine; Scheef, Lukas; Paus, Sebastian; Zimmermann, Nadine; Schild, Hans H.; Klockgether, Thomas; Boecker, Henning

    2016-01-01

    Background & Objective Pain is a common non-motor symptom in Parkinson’s disease. As dopaminergic dysfunction is suggested to affect intrinsic nociceptive processing, this study was designed to characterize laser-induced pain processing in early-stage Parkinson’s disease patients in the dopaminergic OFF state, using a multimodal experimental approach at behavioral, autonomic, imaging levels. Methods 13 right-handed early-stage Parkinson’s disease patients without cognitive or sensory impairment were investigated OFF medication, along with 13 age-matched healthy control subjects. Measurements included warmth perception thresholds, heat pain thresholds, and central pain processing with event-related functional magnetic resonance imaging (erfMRI) during laser-induced pain stimulation at lower (E = 440 mJ) and higher (E = 640 mJ) target energies. Additionally, electrodermal activity was characterized during delivery of 60 randomized pain stimuli ranging from 440 mJ to 640 mJ, along with evaluation of subjective pain ratings on a visual analogue scale. Results No significant differences in warmth perception thresholds, heat pain thresholds, electrodermal activity and subjective pain ratings were found between Parkinson’s disease patients and controls, and erfMRI revealed a generally comparable activation pattern induced by laser-pain stimuli in brain areas belonging to the central pain matrix. However, relatively reduced deactivation was found in Parkinson’s disease patients in posterior regions of the default mode network, notably the precuneus and the posterior cingulate cortex. Conclusion Our data during pain processing extend previous findings suggesting default mode network dysfunction in Parkinson’s disease. On the other hand, they argue against a genuine pain-specific processing abnormality in early-stage Parkinson’s disease. Future studies are now required using similar multimodal experimental designs to examine pain processing in more advanced

  19. Pain and efficacy of local anesthetics for central venous access

    Directory of Open Access Journals (Sweden)

    William C Culp Jr

    2008-11-01

    Full Text Available William C Culp Jr1, Mohammed Yousaf2, Benjamin Lowry1, Timothy C McCowan3, William C Culp21Division of Cardiothoracic Anesthesiology, Scott and White Hospital, The Texas A&M University College of Medicine, Temple, TX, USA; 2Division of Interventional Radiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 3Department of Radiology, University of Mississippi Medical Center, Jackson, MS, USAPurpose: To compare pain during injection and efficacy of analgesia of local anesthetics during central venous line placement.Methods: Sixty-two patients were studied in a randomized, double-blinded prospective fashion. Patients received 1% lidocaine (L, buffered 1% lidocaine (LB, or 2% chloroprocaine (CP injected around the internal jugular vein for procedural analgesia for central venous access. Patients reported pain via a standard linear visual analog scale, with 0 representing no pain and 10 being the worst pain imaginable.Results: Overall patient perception of pain was better with CP and L than LB with mean scores of CP 2.4, L 2.6, LB 4.2. Pain with injection mean scores were CP 2.1, L 2.5, LB 3.2. Pain with catheter placement scores were CP 2.5, L 1.7, LB 3.4. Operator assessment of overall pain values were CP 1.9, L 2.2, LB 3.4. LB consistently scored the worst, though compared with CP, this only reached statistical significance in overall patient pain and pain at catheter insertion compared with L.Conclusion: Though chloroprocaine scored better than lidocaine in 3 of 4 parameters, this trend did not achieve statistical significance. Adding sodium bicarbonate to lidocaine isn’t justified in routine practice, nor is routine replacement of lidocaine with chloroprocaine.Keywords: local anesthesia, analgesia, central venous access, lidocaine, chloroprocaine

  20. Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain.

    Science.gov (United States)

    Kim, Yu Shin; Chu, Yuxia; Han, Liang; Li, Man; Li, Zhe; Lavinka, Pamela Colleen; Sun, Shuohao; Tang, Zongxiang; Park, Kyoungsook; Caterina, Michael J; Ren, Ke; Dubner, Ronald; Wei, Feng; Dong, Xinzhong

    2014-02-19

    The peripheral terminals of primary nociceptive neurons play an essential role in pain detection mediated by membrane receptors like TRPV1, a molecular sensor of heat and capsaicin. However, the contribution of central terminal TRPV1 in the dorsal horn to chronic pain has not been investigated directly. Combining primary sensory neuron-specific GCaMP3 imaging with a trigeminal neuropathic pain model, we detected robust neuronal hyperactivity in injured and uninjured nerves in the skin, soma in trigeminal ganglion, and central terminals in the spinal trigeminal nucleus. Extensive TRPV1 hyperactivity was observed in central terminals innervating all dorsal horn laminae. The central terminal TRPV1 sensitization was maintained by descending serotonergic (5-HT) input from the brainstem. Central blockade of TRPV1 or 5-HT/5-HT3A receptors attenuated central terminal sensitization, excitatory primary afferent inputs, and mechanical hyperalgesia in the territories of injured and uninjured nerves. Our results reveal central mechanisms facilitating central terminal sensitization underlying chronic pain.

  1. Exercise Strengthens Central Nervous System Modulation of Pain in Fibromyalgia

    Science.gov (United States)

    Ellingson, Laura D.; Stegner, Aaron J.; Schwabacher, Isaac J.; Koltyn, Kelli F.; Cook, Dane B.

    2016-01-01

    To begin to elucidate the mechanisms underlying the benefits of exercise for chronic pain, we assessed the influence of exercise on brain responses to pain in fibromyalgia (FM). Complete data were collected for nine female FM patients and nine pain-free controls (CO) who underwent two functional neuroimaging scans, following exercise (EX) and following quiet rest (QR). Brain responses and pain ratings to noxious heat stimuli were compared within and between groups. For pain ratings, there was a significant (p < 0.05) Condition by Run interaction characterized by moderately lower pain ratings post EX compared to QR (d = 0.39–0.41) for FM but similar to ratings in CO (d = 0.10–0.26), thereby demonstrating that exercise decreased pain sensitivity in FM patients to a level that was analogous to pain-free controls. Brain responses demonstrated a significant within-group difference in FM patients, characterized by less brain activity bilaterally in the anterior insula following QR as compared to EX. There was also a significant Group by Condition interaction with FM patients showing less activity in the left dorsolateral prefrontal cortex following QR as compared to post-EX and CO following both conditions. These results suggest that exercise appeared to stimulate brain regions involved in descending pain inhibition in FM patients, decreasing their sensitivity to pain. Thus, exercise may benefit patients with FM via improving the functional capacity of the pain modulatory system. PMID:26927193

  2. Postamputation pain: epidemiology, mechanisms, and treatment

    Directory of Open Access Journals (Sweden)

    Hsu E

    2013-02-01

    Full Text Available Eugene Hsu,1 Steven P Cohen21Johns Hopkins School of Medicine, Baltimore, MD, USA; 2Johns Hopkins School of Medicine and Uniformed Services, University of the Health Sciences, Bethesda, MD, USAAbstract: Postamputation pain (PAP is highly prevalent after limb amputation but remains an extremely challenging pain condition to treat. A large part of its intractability stems from the myriad pathophysiological mechanisms. A state-of-art understanding of the pathophysiologic basis underlying postamputation phenomena can be broadly categorized in terms of supraspinal, spinal, and peripheral mechanisms. Supraspinal mechanisms involve somatosensory cortical reorganization of the area representing the deafferentated limb and are predominant in phantom limb pain and phantom sensations. Spinal reorganization in the dorsal horn occurs after deafferentation from a peripheral nerve injury. Peripherally, axonal nerve damage initiates inflammation, regenerative sprouting, and increased "ectopic" afferent input which is thought by many to be the predominant mechanism involved in residual limb pain or neuroma pain, but may also contribute to phantom phenomena. To optimize treatment outcomes, therapy should be individually tailored and mechanism based. Treatment modalities include injection therapy, pharmacotherapy, complementary and alternative therapy, surgical therapy, and interventions aimed at prevention. Unfortunately, there is a lack of high quality clinical trials to support most of these treatments. Most of the randomized controlled trials in PAP have evaluated medications, with a trend for short-term efficacy noted for ketamine and opioids. Evidence for peripheral injection therapy with botulinum toxin and pulsed radiofrequency for residual limb pain is limited to very small trials and case series. Mirror therapy is a safe and cost-effective alternative treatment modality for PAP. Neuromodulation using implanted motor cortex stimulation has shown a trend

  3. Cancer pain: A critical review of mechanism-based classification and physical therapy management in palliative care

    Directory of Open Access Journals (Sweden)

    Senthil P Kumar

    2011-01-01

    Full Text Available Mechanism-based classification and physical therapy management of pain is essential to effectively manage painful symptoms in patients attending palliative care. The objective of this review is to provide a detailed review of mechanism-based classification and physical therapy management of patients with cancer pain. Cancer pain can be classified based upon pain symptoms, pain mechanisms and pain syndromes. Classification based upon mechanisms not only addresses the underlying pathophysiology but also provides us with an understanding behind patient′s symptoms and treatment responses. Existing evidence suggests that the five mechanisms - central sensitization, peripheral sensitization, sympathetically maintained pain, nociceptive and cognitive-affective - operate in patients with cancer pain. Summary of studies showing evidence for physical therapy treatment methods for cancer pain follows with suggested therapeutic implications. Effective palliative physical therapy care using a mechanism-based classification model should be tailored to suit each patient′s findings, using a biopsychosocial model of pain.

  4. Methods to measure peripheral and central sensitization using quantitative sensory testing: A focus on individuals with low back pain.

    Science.gov (United States)

    Starkweather, Angela R; Heineman, Amy; Storey, Shannon; Rubia, Gil; Lyon, Debra E; Greenspan, Joel; Dorsey, Susan G

    2016-02-01

    Quantitative sensory testing can be used to assess peripheral and central sensitization; important factors that contribute to the individual's experience of pain and disability. Many studies use quantitative sensory testing in patients with low back pain to detect alterations in pain sensitivity, however, because investigators employ different protocols, interpretation of findings across studies can become problematic. The purpose of this article is to propose a standardized method of testing peripheral and central pain sensitization in patients with low back pain. Video clips are provided to demonstrate correct procedures for measuring the response to experimental pain using mechanical, thermal and pressure modalities. As nurse researchers and clinicians increase utilization of quantitative sensory testing to examine pain phenotypes, it is anticipated that more personalized methods for monitoring the trajectory of low back pain and response to treatment will improve outcomes for this patient population.

  5. The role of sleep problems in central pain processing in rheumatoid arthritis

    Science.gov (United States)

    Lee, Yvonne C.; Lu, Bing; Edwards, Robert R.; Wasan, Ajay D.; Nassikas, Nicholas J.; Clauw, Daniel J.; Solomon, Daniel H.; Karlson, Elizabeth W.

    2012-01-01

    Objective Among rheumatoid arthritis (RA) patients, pain may exist out of proportion to peripheral inflammation. This observation suggests that central nervous system pain amplification mechanisms, such as diminished conditioned pain modulation (CPM), may play a role in enhancing pain perception among some RA patients. We examined CPM, pressure pain threshold and pressure pain tolerance among RA patients compared to controls. Methods Fifty-eight female RA patients and 54 age-matched controls without chronic pain underwent quantitative sensory testing (QST) to assess CPM, pressure pain threshold and pressure pain tolerance. CPM was induced using a cold water bath, and pain threshold (when patients first felt pain) and tolerance (when pain was too much to bear) were assessed with an algometer. Associations between RA and QST measures were analyzed using linear regression. Sleep problems, mental health and inflammation were assessed as mediators of the relationship between RA and QST measures. Results Median CPM levels were 0.5 kg/cm2 (interquartile range (IQR) −0.1, 1.6) among RA patients compared to 1.5 kg/cm2 (IQR −0.1, 2.5) among controls (P = 0.04). Relative to controls, RA patients had lower pain threshold and tolerance at the wrists (P ≤ 0.05). Compared to controls, RA patients had greater problems with sleep, catastrophizing, depression and anxiety (P < 0.0001). Mediation analyses suggested that low CPM levels may be partially attributable to sleep disturbance (P = 0.04). Conclusion RA patients have impaired CPM relative to pain-free controls. Sleep problems may mediate the association between RA and attenuated CPM. PMID:23124650

  6. Potential mechanisms of neuropathic pain in diabetes.

    Science.gov (United States)

    Calcutt, Nigel A

    2002-01-01

    Abnormal sensations and pain are features of approximately 10% of all cases of diabvetic neuropathy and can cause marked diminution in the quality of life for these patients. The quality and distribution of pain are variable, although descriptions of burning pain in the hands and feet are commonly reported. Like other neuropathic pain states, painful diabetic neuropathy has an unknown pathogenesis and, in many cases, is not alleviated by nonsteriodal anti-inflammatory drugs or opiates. In the last decase, a number of behavioral and physiologic studies have revealed indices of sensory dysfunction in animal models of diabetes. These include hyperalgesia to mechanical and noxious chemical stimuli and allodynia to light touch. Animal models of painful diabetic neuropathy have been used to investigate the therapeutic potential of a range of experimental agents and also to explore potential etiologic mechanisms. There is relatively little evidence to suggest that the peripheral sensory nerves of diabetic rodents exhibit spontaneous activity or increased responsiveness to peripheral stimuli. Indeed, the weight of eveidence suggests that sensory input to the spinal cord is decreased rather than increased in diabetic rodents. Aberrant spinal or supraspinal modulation of sensory processing may therefore be involved in generating allodynia and hyperalgesia in these models. Studies have supported a role for spinally mediated hyeralgesia in diabetic rats that may reflect either a response to diminished peripheral input or a consequence of hyperglycemia on local or descending modulatory systems. Elucidating the affects of diabetes on spinal sensory processing may assist development of novel therapeutic strategies for preventing and alleviating painful diabetic neuropathy.

  7. Central charges in regular mechanics

    CERN Document Server

    Cabo-Montes de Oca, Alejandro; Villanueva, V M

    1997-01-01

    We consider the algebra associated to a group of transformations which are symmetries of a regular mechanical system (i.e. system free of constraints). For time dependent coordinate transformations we show that a central extension may appear at the classical level which is coordinate and momentum independent. A cochain formalism naturally arises in the argument and extends the usual configuration space cochain concepts to phase space.

  8. Mechanisms and management of diabetic painful distal symmetrical polyneuropathy.

    Science.gov (United States)

    Tesfaye, Solomon; Boulton, Andrew J M; Dickenson, Anthony H

    2013-09-01

    Although a number of the diabetic neuropathies may result in painful symptomatology, this review focuses on the most common: chronic sensorimotor distal symmetrical polyneuropathy (DSPN). It is estimated that 15-20% of diabetic patients may have painful DSPN, but not all of these will require therapy. In practice, the diagnosis of DSPN is a clinical one, whereas for longitudinal studies and clinical trials, quantitative sensory testing and electrophysiological assessment are usually necessary. A number of simple numeric rating scales are available to assess the frequency and severity of neuropathic pain. Although the exact pathophysiological processes that result in diabetic neuropathic pain remain enigmatic, both peripheral and central mechanisms have been implicated, and extend from altered channel function in peripheral nerve through enhanced spinal processing and changes in many higher centers. A number of pharmacological agents have proven efficacy in painful DSPN, but all are prone to side effects, and none impact the underlying pathophysiological abnormalities because they are only symptomatic therapy. The two first-line therapies approved by regulatory authorities for painful neuropathy are duloxetine and pregabalin. α-Lipoic acid, an antioxidant and pathogenic therapy, has evidence of efficacy but is not licensed in the U.S. and several European countries. All patients with DSPN are at increased risk of foot ulceration and require foot care, education, and if possible, regular podiatry assessment.

  9. Peripheral Mechanisms of Dental Pain: The Role of Substance P

    Directory of Open Access Journals (Sweden)

    Paola Sacerdote

    2012-01-01

    Full Text Available Current evidence supports the central role of neuropeptides in the molecular mechanisms underlying dental pain. In particular, substance P, a neuropeptide produced in neuron cell bodies localised in dorsal root and trigeminal ganglia, contributes to the transmission and maintenance of noxious stimuli and inflammatory processes. The major role of substance P in the onset of dental pain and inflammation is increasingly being recognised. Well-grounded experimental and clinical observations have documented an increase in substance P concentration in patients affected by caries, pulpitis, or granulomas and in those undergoing standard orthodontic or orthodontic/dental care procedures. This paper focuses on the role of substance P in the induction and maintenance of inflammation and dental pain, in order to define future lines of research for the evaluation of therapeutic strategies aimed at modulating the complex effects of this mediator in oral tissues.

  10. Peripheral mechanisms of dental pain: the role of substance P.

    Science.gov (United States)

    Sacerdote, Paola; Levrini, Luca

    2012-01-01

    Current evidence supports the central role of neuropeptides in the molecular mechanisms underlying dental pain. In particular, substance P, a neuropeptide produced in neuron cell bodies localised in dorsal root and trigeminal ganglia, contributes to the transmission and maintenance of noxious stimuli and inflammatory processes. The major role of substance P in the onset of dental pain and inflammation is increasingly being recognised. Well-grounded experimental and clinical observations have documented an increase in substance P concentration in patients affected by caries, pulpitis, or granulomas and in those undergoing standard orthodontic or orthodontic/dental care procedures. This paper focuses on the role of substance P in the induction and maintenance of inflammation and dental pain, in order to define future lines of research for the evaluation of therapeutic strategies aimed at modulating the complex effects of this mediator in oral tissues.

  11. Neuroinflammatory Mechanisms Linking Pain and Depression.

    Science.gov (United States)

    Burke, Nikita N; Finn, David P; Roche, Michelle

    2015-01-01

    Depression and chronic pain have been estimated to co-occur in up to 80% of patients suffering from these disorders, with this co-morbidity being more disabling and more expensive to both patients and society than either disorder alone. A number of neural substrates have been proposed to underlie this association; however, there has been increased interest and support for a role of neuroimmune and neuroinflammatory mechanisms as key players in this dyad. This chapter will provide an overview of the clinical and preclinical data supporting a role for neuroimmune alterations in depression-pain co-morbidity. We propose that such changes may impact on the functioning of key brain regions modulating emotional and nociceptive processing, thus resulting in the behavioural, psychological and physical symptoms observed in patients exhibiting depression and co-morbid pain.

  12. CURRENT IDEAS ABOUT THE PATHOGENETIC MECHANISMS OF PAIN IN OSTEOARTHROSIS

    OpenAIRE

    2014-01-01

    The literature review presents the current idea about the mechanisms of chronic pain. Experimental and clinical studies of the mechanism of chronic pain in osteoarthrosis (OA), which show that dysfunction of pain systems themselves (the so-called dysfunctional pain) along with the nociceptive mechanisms caused by chronic inflammation and degenerative changes in the joint area plays an important role in the chronization of pain syndrome, are considered in detail. Identification of the dysfunct...

  13. Motor cortex stimulation reduces hyperalgesia in an animal model of central pain.

    Science.gov (United States)

    Lucas, Jessica M; Ji, Yadong; Masri, Radi

    2011-06-01

    Electrical stimulation of the primary motor cortex has been used since 1991 to treat chronic neuropathic pain. Since its inception, motor cortex stimulation (MCS) treatment has had varied clinical outcomes. Until this point, there has not been a systematic study of the stimulation parameters that most effectively treat chronic pain, or of the mechanisms by which MCS relieves pain. Here, using a rodent model of central pain, we perform a systematic study of stimulation parameters used for MCS and investigate the mechanisms by which MCS reduces hyperalgesia. Specifically, we study the role of the inhibitory nucleus zona incerta (ZI) in mediating the analgesic effects of MCS. In animals with mechanical and thermal hyperalgesia, we find that stimulation at 50 μA, 50 Hz, and 300 μs square pulses for 30 minutes is sufficient to reverse mechanical and thermal hyperalgesia. We also find that stimulation of the ZI mimics the effects of MCS and that reversible inactivation of ZI blocks the effects of MCS. These findings suggest that the reduction of hyperalgesia may be due to MCS effects on ZI. In an animal model of central pain syndrome, motor cortex stimulation reduces hyperalgesia by activating zona incerta and therefore restoring inhibition in the thalamus.

  14. Early evoked pain or dysesthesia is a predictor of central poststroke pain.

    Science.gov (United States)

    Klit, Henriette; Hansen, Anne P; Marcussen, Ninna S; Finnerup, Nanna B; Jensen, Troels S

    2014-12-01

    Central poststroke pain (CPSP) is a central neuropathic pain condition caused by a cerebrovascular lesion affecting the central somatosensory nervous system. Once developed, CPSP is difficult to treat, so there is an interest in identifying stroke patients at risk for the development of CPSP. This study examined if sensory abnormalities, including evoked dysesthesia, allodynia, or hyperalgesia to static and dynamic touch, cold, and pinprick, at stroke onset are a predictor for the development of CPSP. Consecutive stroke patients were recruited from a large prospective study of poststroke pain in Aarhus, Denmark, between 2007 and 2008. Patients underwent a structured pain interview and a standardized sensory examination within 4 days of admission, and a structured telephone interview was conducted after 3 and 6months. Patients who developed poststroke pain in the affected side without any other plausible cause were classified as having possible CPSP. A total of 275 stroke patients completed the study, and 29 patients (10.5%) were classified as having possible CPSP. The diagnosis was confirmed by a clinical examination in 15 of 17 patients, corresponding to a prevalence of 8.3%. The presence of allodynia, hyperalgesia, or dysesthesia in response to the sensory examination at stroke onset increased the odds for CPSP at 6months by 4.6 (odds ratio; 95% confidence interval 1.5-13.9). The combination of reduced or absent sensation to pinprick or cold and early evoked pain or dysesthesia at onset increased odds by 8.0 (odds ratio; 95% confidence interval 2.6-24.8). In conclusion, early evoked pain or dysesthesia is a predictor for CPSP.

  15. Central poststroke pain: a population-based study.

    Science.gov (United States)

    Klit, Henriette; Finnerup, Nanna Brix; Andersen, Grethe; Jensen, Troels Staehelin

    2011-04-01

    Central poststroke pain (CPSP) is a specific pain condition arising as a direct consequence of a cerebrovascular lesion. There is limited knowledge about the epidemiology and clinical characteristics of this often neglected but important consequence of stroke. In this population-based study, a questionnaire was sent out to all (n=964) stroke patients identified through the Danish National Indicator Project Stroke Database in Aarhus County, Denmark, between March 2004 and February 2005. All surviving patients who fulfilled 4 questionnaire criteria for possible CPSP (n=51) were selected for further clinical examination, and their pain was classified by using stringent and well-defined criteria and a detailed, standardized clinical examination. The minimum prevalence of definite or probable CPSP in this population is 7.3% and the prevalence of CPSP-like dysesthesia or pain is 8.6%. Pinprick hyperalgesia was present in 57%, cold allodynia in 40%, and brush-evoked dysesthesia in 51% of patients with CPSP. Because of its negative impact on quality of life and rehabilitation, pain is an important symptom to assess in stroke survivors.

  16. Mechanism-based classification of pain for physical therapy management in palliative care: A clinical commentary

    Directory of Open Access Journals (Sweden)

    Senthil P Kumar

    2011-01-01

    Full Text Available Pain relief is a major goal for palliative care in India so much that most palliative care interventions necessarily begin first with pain relief. Physical therapists play an important role in palliative care and they are regarded as highly proficient members of a multidisciplinary healthcare team towards management of chronic pain. Pain necessarily involves three different levels of classification-based upon pain symptoms, pain mechanisms and pain syndromes. Mechanism-based treatments are most likely to succeed compared to symptomatic treatments or diagnosis-based treatments. The objective of this clinical commentary is to update the physical therapists working in palliative care, on the mechanism-based classification of pain and its interpretation, with available therapeutic evidence for providing optimal patient care using physical therapy. The paper describes the evolution of mechanism-based classification of pain, the five mechanisms (central sensitization, peripheral neuropathic, nociceptive, sympathetically maintained pain and cognitive-affective are explained with recent evidence for physical therapy treatments for each of the mechanisms.

  17. Pain mechanisms and ultrasonic inflammatory activity as prognostic factors in patients with psoriatic arthritis

    DEFF Research Database (Denmark)

    Højgaard, Pil; Christensen, Robin; Dreyer, Lene

    2016-01-01

    ) and erroneous treatments. Ultrasonography (US) is a highly sensitive method to detect tissue inflammation. Evaluating pain mechanisms in relation to US measures may prove valuable in predicting response to treatment in PsA. AIMS: To study the association and prognostic value of pain mechanisms, ultrasonic...... activity and clinical outcomes in patients with PsA who intensify antirheumatic treatment. METHODS AND ANALYSES: 100 participants >18 years of age with PsA who initiate or switch antirheumatic treatment (biologicals and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs......INTRODUCTION: Persistent pain is a major concern for patients with psoriatic arthritis (PsA). Pain may be due to inflammatory activity or augmented central pain processing. Unawareness of the origin and mechanisms of pain can lead to misinterpretation of disease activity (by composite scores...

  18. A novel use for testosterone to treat central sensitization of chronic pain in fibromyalgia patients.

    Science.gov (United States)

    White, Hillary D; Robinson, Thomas D

    2015-08-01

    Fibromyalgia is a diffuse chronic pain condition that occurs predominantly in women and may be under-reported in men. Symptoms include a loss of feeling of well-being and generalized widespread flu-like muscle aches and pain that fail to resolve due to central sensitization of nociceptive neurons. It has commonalities with a myriad of other chronic pain conditions which include PTSD, "Gulf War Syndrome", and various stress-induced conditions caused, for example, by viral infection, emotional or physical stress, trauma, combat, accident or surgery. It is not understood why some individuals are susceptible to this condition and others are not. White et al., elsewhere in this issue, present a clinical feasibility study designed to test the hypothesis that 1) low or deficient testosterone serum levels are linked to a high risk for an inflamed nociceptive nervous system and resultant chronic pain states, and 2) a testosterone transdermal gel applied once a day by fibromyalgia patients can be an effective therapeutic against chronic pain. Here, a short profile of fibromyalgia is provided along with a brief summary of best practices currently recommended by clinical specialists. The link between testosterone and pain is then discussed, with an overview of scientific studies that lay the foundation for testosterone as a possible important additional therapeutic that has the potential to be safely administered and effective but also avoid the adverse effects of other therapeutics. Finally, novel mechanisms by which testosterone therapy is likely to down-modulate pain signaling are proposed.

  19. Perturbed connectivity of the amygdala and its subregions with the central executive and default mode networks in chronic pain.

    Science.gov (United States)

    Jiang, Ying; Oathes, Desmond; Hush, Julia; Darnall, Beth; Charvat, Mylea; Mackey, Sean; Etkin, Amit

    2016-09-01

    Maladaptive responses to pain-related distress, such as pain catastrophizing, amplify the impairments associated with chronic pain. Many of these aspects of chronic pain are similar to affective distress in clinical anxiety disorders. In light of the role of the amygdala in pain and affective distress, disruption of amygdalar functional connectivity in anxiety states, and its implication in the response to noxious stimuli, we investigated amygdala functional connectivity in 17 patients with chronic low back pain and 17 healthy comparison subjects, with respect to normal targets of amygdala subregions (basolateral vs centromedial nuclei), and connectivity to large-scale cognitive-emotional networks, including the default mode network, central executive network, and salience network. We found that patients with chronic pain had exaggerated and abnormal amygdala connectivity with central executive network, which was most exaggerated in patients with the greatest pain catastrophizing. We also found that the normally basolateral-predominant amygdala connectivity to the default mode network was blunted in patients with chronic pain. Our results therefore highlight the importance of the amygdala and its network-level interaction with large-scale cognitive/affective cortical networks in chronic pain, and help link the neurobiological mechanisms of cognitive theories for pain with other clinical states of affective distress.

  20. Phantom limb pain: a review of the literature on attributes and potential mechanisms.

    Science.gov (United States)

    Hill, A

    1999-02-01

    This study presents a review of the literature on the attributes and potential mechanisms involved in phantom limb pain, encompassing studies describing pain in the residual limb, phantom sensation and phantom limb pain, and the difficulties that may arise when making these distinctions. A variety of theories have been proposed to explain causal mechanisms for phantom limb pain. Conceptually, research into phantom limb pain is informed by the particular theory of chronic pain that is dominant at the time the research is undertaken. For example, early physiological theories on the etiology of phantom limb pain were grounded in specificity or pattern theories of pain. Later physiological research was based on the framework provided by Gate Control Theory and focused on identifying peripheral, spinal, and central neural mechanisms. Psychological explanations were grounded in psychoanalytic or personality theories of chronic pain which propose that phantom limb pain results from pre-amputation psychological disturbance. Despite numerous studies examining phantom limb pain, much of this research has both conceptual and methodological shortcomings. As such, the application of these research findings to clinical practice has limited utility.

  1. Pregabalin and placebo responders show different effects on central pain processing in chronic pancreatitis patients

    Directory of Open Access Journals (Sweden)

    Bouwense SA

    2015-07-01

    -generating study provides the first evidence that pain relief with pregabalin is associated with anti-hyperalgesic effects and increased endogenous inhibitory modulation. No such effects were observed in patients experiencing pain relief with the placebo treatment. The mechanisms underlying analgesic response to placebo vs drug treatments are different and, together with their interactions, deserve further study.Keywords: chronic pancreatitis, pregabalin, placebo, chronic pain treatment, quantitative sensory testing, central sensitization

  2. Cortical excitability changes after high-frequency repetitive transcranial magnetic stimulation for central poststroke pain.

    Science.gov (United States)

    Hosomi, Koichi; Kishima, Haruhiko; Oshino, Satoru; Hirata, Masayuki; Tani, Naoki; Maruo, Tomoyuki; Yorifuji, Shiro; Yoshimine, Toshiki; Saitoh, Youichi

    2013-08-01

    Central poststroke pain (CPSP) is one of the most refractory chronic pain syndromes. Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has been demonstrated to provide moderate pain relief for CPSP. However, the mechanism underlying the pain relief remains unclear. The objective of this study was to assess changes in cortical excitability in patients with intractable CPSP before and after rTMS of the primary motor cortex. Subjects were 21 patients with CPSP of the hand who underwent rTMS. The resting motor threshold, the amplitude of the motor evoked potential, duration of the cortical silent period, short interval intracortical inhibition, and intracortical facilitation were measured as parameters of cortical excitability before and after navigation-guided 5 Hz rTMS of the primary motor cortex corresponding to the painful hand. Pain reduction from rTMS was assessed with a visual analog scale. The same parameters were measured in both hemispheres of 8 healthy controls. Eight of 21 patients experienced ≥ 30% pain reduction after rTMS (responders). The resting motor threshold in the patients was higher than those in the controls at baseline (P=.035). Intracortical facilitation in the responders was lower than in the controls and the nonresponders at baseline (P=.035 and P=.019), and significantly increased after rTMS (P=.039). There were no significant differences or changes in the other parameters. Our findings suggest that restoration of abnormal cortical excitability might be one of the mechanisms underlying pain relief as a result of rTMS in CPSP.

  3. Differential effect of ketamine and lidocaine on spontaneous and mechanical evoked pain in patients with nerve injury pain

    DEFF Research Database (Denmark)

    Gottrup, Hanne; Bach, Flemming Winther; Juhl, Gitte Irene;

    2006-01-01

    BACKGROUND: The mechanisms underlying neuropathic pain are incompletely understood. Targeting specific molecular mechanisms in the pain signaling system may assist in understanding key features in neuropathic pains such as allodynia. This study examined the effect of systemically administered ket...

  4. Mechanisms of acupuncture analgesia: effective therapy for musculoskeletal pain?

    Science.gov (United States)

    Staud, Roland

    2007-12-01

    Acupuncture (AP) is effective for the treatment of postoperative and chemotherapy-induced nausea/vomiting and for postoperative dental pain. Several recent randomized trials have provided strong evidence for beneficial AP effects on chronic low-back pain and pain from knee osteoarthritis. For many other chronic pain conditions, including headaches, neck pain, and fibromyalgia, the evidence supporting AP's efficacy is less convincing. AP's effects on experimental pain appear to be mediated by analgesic brain mechanisms through the release of neurohumoral factors, some of which can be inhibited by the opioid antagonist naloxone. In contrast to placebo analgesia, AP-related pain relief takes considerable time to develop and to resolve. Thus, some of the long-term effects of AP analgesia cannot be explained by placebo mechanisms. Furthermore, it appears that some forms of AP are more effective for providing analgesia than others. Particularly, electro-AP seems best to activate powerful opioid and non-opioid analgesic mechanisms.

  5. Chronic musculoskeletal pain: review of mechanisms and biochemical biomarkers as assessed by the microdialysis technique

    Directory of Open Access Journals (Sweden)

    Gerdle B

    2014-06-01

    Full Text Available Björn Gerdle,1,2 Bijar Ghafouri,1,3 Malin Ernberg,4 Britt Larsson1,21Rehabilitation Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; 2Pain and Rehabilitation Centre, County Council of Östergötland, Linköping, Sweden; 3Rehabilitation Medicine, Department of Medicine and Health Sciences, Linköping University, Linköping, Sweden; 4Department of Dental Medicine, Section of Orofacial Pain and Jaw Function, Karolinska Institutet, Huddinge, SwedenAbstract: Chronic musculoskeletal pain conditions are multifaceted, and approximately 20% of the adult population lives with severe chronic pain, with a higher prevalence in women and in lower income groups. Chronic pain is influenced by and interacts with physical, emotional, psychological, and social factors, and a biopsychosocial framework is increasingly applied in clinical practice. However, there is still a lack of assessment procedures based on the activated neurobiological pain mechanisms (ie, the biological part of the biopsychosocial model of pain, which may be a necessary step for further optimizing outcomes after treatments for patients with chronic pain. It has been suggested that chronic pain conditions are mainly driven by alterations in the central nervous system with little or no peripheral stimuli or nociception. In contrast, other authors argue that such central alterations are driven by peripheral alterations and nociceptive input. Microdialysis is an in vivo method for studying local tissue alterations and allows for sampling of substances in the interstitium of the muscle, where nociceptor free nerve endings are found close to the muscle fibers. The extracellular matrix plays a key role in physiologic functions of cells, including the primary afferent nociceptor. The present review mainly concerns the results of microdialysis studies and how they can contribute to the understanding of activated peripheral nociceptive and pain

  6. Current views of the development of pain syndrome mechanisms in patients with osteoarthrosis. Rational pharmacotherapy

    Directory of Open Access Journals (Sweden)

    E. V. Igolkina

    2014-01-01

    Full Text Available The paper outlines the current views on mechanisms for pain development in osteoarthrosis (OA. The problem of analgesia in OA remains to be solved, which gives rise to a more careful study of the mechanisms in OA. Whether peripheral somatosensory nerve damage occurs in OA is the subject of careful investigation and dispute. The paper gives the results of studies of the neurogenic component of pain in OA patients. There is sufficient evidence for the presence of sensory anomalies accompanying pain in OA. The clinical use of questionnaires to detect neuropathic pain may assist in identifying central sensitization in patients with OA. Medicaments for the symptomatic therapy of pain are characterized.

  7. Mechanical pain sensitivity and the severity of chronic neck pain and disability are not modulated across the menstrual cycle

    OpenAIRE

    2013-01-01

    Despite the high prevalence of neck pain among women, menstrual effects on regional pain outcomes have not been investigated in this clinical population. This study evaluated menstrual effects on mechanical pain sensitivity (Pressure Pain Threshold; PPT), neck pain intensity (Numeric Pain Rating Scale; NPRS) and neck-related disability (Neck Disability Index; NDI) in 22 normally menstruating (NM) and 17 hormonal contraceptive (HC) users with chronic neck pain. Sex hormones, PPT, and NDI were ...

  8. How to explain central sensitization to patients with 'unexplained' chronic musculoskeletal pain : Practice guidelines

    NARCIS (Netherlands)

    Nijs, Jo; van Wilgen, C. Paul; Van Oosterwijck, Jessica; van Ittersum, Miriam; Meeus, Mira

    2011-01-01

    Central sensitization provides an evidence-based explanation for many cases of 'unexplained' chronic musculoskeletal pain. Prior to commencing rehabilitation in such cases, it is crucial to change maladaptive illness perceptions, to alter maladaptive pain cognitions and to reconceptualise pain. This

  9. Mechanical therapy for low back pain.

    Science.gov (United States)

    Guild, Donald Grant

    2012-09-01

    Physical therapy and manual medicine for low back pain encompass many different treatment modalities. There is a vast variety of techniques that physical therapists commonly use in the treatment of low back pain. Some of the therapies include, but are certainly not limited to, education, exercise, lumbar traction, manual manipulation, application of heat, cryotherapy, and ultrasonography. Many of these approaches are discussed specifically in this article.

  10. Reaction to topical capsaicin in spinal cord injury patients with and without central pain

    DEFF Research Database (Denmark)

    Finnerup, Nanna Brix; Pedersen, Louise H.; Terkelsen, Astrid J.

    2007-01-01

    Central neuropathic pain is a debilitating and frequent complication to spinal cord injury (SCI). Excitatory input from hyperexcitable cells around the injured grey matter zone is suggested to play a role for central neuropathic pain felt below the level of a spinal cord injury. Direct evidence...... of a spinal cord injury which already is hyperexcitable, would cause enhanced responses in patients with central pain at the level of injury compared to patients without neuropathic pain and healthy controls. Touch, punctuate stimuli, cold stimuli and topical capsaicin was applied above, at, and below injury...... level in 10 SCI patients with central pain below a thoracic injury, in 10 SCI patients with a thoracic injury but without neuropathic pain, and in corresponding areas in 10 healthy control subjects. The study found increased responses to touch at injury level compared to controls (p = 0...

  11. Detection of central circuits implicated in the formation of novel pain memories

    Directory of Open Access Journals (Sweden)

    Upadhyay J

    2016-09-01

    Full Text Available Jaymin Upadhyay,1 Julia Granitzka,1 Thomas Bauermann,2 Ulf Baumgärtner,3 Markus Breimhorst,1 Rolf-Detlef Treede,3 Frank Birklein1 1Department of Neurology, 2Department of Neuroradiology, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, 3Department of Neurophysiology, Center for Biomedicine and Medical Technology Mannheim (CBTM, Heidelberg University, Mannheim, Germany Abstract: Being able to remember physically and emotionally painful events in one’s own past may shape behavior, and can create an aversion to a variety of situations. Pain imagination is a related process that may include recall of past experiences, in addition to production of sensory and emotional percepts without external stimuli. This study aimed to understand 1 the central nervous system processes that underlie pain imagination, 2 the retrieval of pain memories, and 3 to compare the latter with visual object memory. These goals were achieved by longitudinally investigating brain function with functional magnetic resonance imaging in a unique group of healthy volunteers who had never experienced tooth pain. In these subjects, we compared brain responses elicited during three experimental conditions in the following order: imagination of tooth pain (pain imagination, remembering one’s own house (object memory, and remembrance of tooth pain following an episode of induced acute tooth pain (pain memory. Key observations stemming from group-level conjunction analyses revealed common activation in the posterior parietal cortex for both pain imagination and pain memory, while object and pain memory each had strong activation predominantly within the middle frontal gyrus. When contrasting pain imagination and memory, significant activation differences were observed in subcortical structures (ie, parahippocampus – pain imagination > pain memory; midbrain – pain memory > pain imagination. Importantly, these findings were observed in the presence of

  12. Beep tones attenuate pain following Pavlovian conditioning of an endogenous pain control mechanism.

    Directory of Open Access Journals (Sweden)

    Raymonde Scheuren

    Full Text Available Heterotopic noxious counter-stimulation (HNCS is commonly used to study endogenous pain control systems. The resulting pain inhibition is primarily based on spinal cord-brainstem loops. Recently, functional imaging studies have shown that limbic structures like the anterior cingulate cortex and amygdala are also implicated. Since these structures are involved in learning processes, it is possible that the HNCS-induced pain inhibition may depend on specific cues from the environment that have been associated with pain reduction through associative learning. We investigated the influence of Pavlovian conditioning on HNCS-induced pain inhibition in 32 healthy subjects by using a differential conditioning paradigm in which two different acoustic stimuli were either repeatedly paired or unpaired with HNCS. Series of noxious electrical pulse trains delivered to the non-dominant foot served as test stimuli. Diffuse noxious inhibitory control (DNIC-like effects were induced by concurrent application of tonic HNCS (immersion of the contralateral hand in ice water. Subjective pain intensity and pain unpleasantness ratings and electromyographic recordings of the facial corrugator muscle and the nocifensive RIII flexion reflex were used to measure changes in pain sensitivity. HNCS induced significant pain and reflex inhibitions. In the post-conditioning phase, only the paired auditory cue was able to significantly reduce pain perceptions and corrugator muscle activity. No conditioned effect could be observed in RIII reflex responses. Our results indicate that the functional state of endogenous pain control systems may depend on associative learning processes that, like in the present study, may lead to an attenuation of pain perception. Similar albeit opposite conditioning of pain control mechanisms may significantly be involved in the exacerbation and chronification of pain states.

  13. Beep tones attenuate pain following Pavlovian conditioning of an endogenous pain control mechanism.

    Science.gov (United States)

    Scheuren, Raymonde; Anton, Fernand; Erpelding, Nathalie; Michaux, Gilles

    2014-01-01

    Heterotopic noxious counter-stimulation (HNCS) is commonly used to study endogenous pain control systems. The resulting pain inhibition is primarily based on spinal cord-brainstem loops. Recently, functional imaging studies have shown that limbic structures like the anterior cingulate cortex and amygdala are also implicated. Since these structures are involved in learning processes, it is possible that the HNCS-induced pain inhibition may depend on specific cues from the environment that have been associated with pain reduction through associative learning. We investigated the influence of Pavlovian conditioning on HNCS-induced pain inhibition in 32 healthy subjects by using a differential conditioning paradigm in which two different acoustic stimuli were either repeatedly paired or unpaired with HNCS. Series of noxious electrical pulse trains delivered to the non-dominant foot served as test stimuli. Diffuse noxious inhibitory control (DNIC)-like effects were induced by concurrent application of tonic HNCS (immersion of the contralateral hand in ice water). Subjective pain intensity and pain unpleasantness ratings and electromyographic recordings of the facial corrugator muscle and the nocifensive RIII flexion reflex were used to measure changes in pain sensitivity. HNCS induced significant pain and reflex inhibitions. In the post-conditioning phase, only the paired auditory cue was able to significantly reduce pain perceptions and corrugator muscle activity. No conditioned effect could be observed in RIII reflex responses. Our results indicate that the functional state of endogenous pain control systems may depend on associative learning processes that, like in the present study, may lead to an attenuation of pain perception. Similar albeit opposite conditioning of pain control mechanisms may significantly be involved in the exacerbation and chronification of pain states.

  14. Psychological and neural mechanisms of the affective dimension of pain.

    Science.gov (United States)

    Price, D D

    2000-06-09

    The affective dimension of pain is made up of feelings of unpleasantness and emotions associated with future implications, termed secondary affect. Experimental and clinical studies show serial interactions between pain sensation intensity, pain unpleasantness, and secondary affect. These pain dimensions and their interactions relate to a central network of brain structures that processes nociceptive information both in parallel and in series. Spinal pathways to limbic structures and medial thalamic nuclei provide direct inputs to brain areas involved in affect. Another source is from spinal pathways to somatosensory thalamic and cortical areas and then through a cortico-limbic pathway. The latter integrates nociceptive input with contextual information and memory to provide cognitive mediation of pain affect. Both direct and cortico-limbic pathways converge on the same anterior cingulate cortical and subcortical structures whose function may be to establish emotional valence and response priorities.

  15. Neuronal mechanisms for pain-induced aversion behavioral studies using a conditioned place aversion test.

    Science.gov (United States)

    Minami, Masabumi

    2009-01-01

    Pain consists of sensory discriminative and negative affective components. Although the neural systems responsible for the sensory component of pain have been studied extensively, the neural basis of the affective component is not well understood. Recently, behavioral studies using conditioned place aversion (CPA) tests have successfully elucidated the neural circuits and mechanisms underlying the negative affective component of pain. Excitotoxic lesions of the anterior cingulate cortex (ACC), central amygdaloid nucleus, basolateral amygdaloid nucleus (BLA), or bed nucleus of the stria terminalis (BNST) suppressed intraplantar formalin-induced aversive responses. Glutamatergic transmission within the ACC and BLA via NMDA receptors was shown to play a critical role in the affective component of pain. In the BNST, especially its ventral part, noradrenergic transmission via beta-adrenergic receptors was demonstrated as important for pain-induced aversion. Because persistent pain is frequently associated with psychological and emotional dysfunction, studies of the neural circuits and the molecular mechanisms involved in the affective component of pain may have considerable clinical importance in the treatment of chronic pain.

  16. Caloric Vestibular Stimulation Reduces Pain and Somatoparaphrenia in a Severe Chronic Central Post-Stroke Pain Patient: A Case Study.

    Science.gov (United States)

    Spitoni, Grazia Fernanda; Pireddu, Giorgio; Galati, Gaspare; Sulpizio, Valentina; Paolucci, Stefano; Pizzamiglio, Luigi

    2016-01-01

    Central post-stroke pain is a neuropathic syndrome characterized by intolerable contralesional pain and, in rare cases, somatic delusions. To date, there is limited evidence for the effective treatments of this disease. Here we used caloric vestibular stimulation to reduce pain and somatoparaphrenia in a 57-year-old woman suffering from central post-stroke pain. Resting-state functional magnetic resonance imaging was used to assess the neurological effects of this treatment. Following vestibular stimulation we observed impressive improvements in motor skills, pain, and somatic delusions. In the functional connectivity study before the vestibular stimulation, we observed differences in the patient's left thalamus functional connectivity, with respect to the thalamus connectivity of a control group (N = 20), in the bilateral cingulate cortex and left insula. After the caloric stimulation, the left thalamus functional connectivity with these regions, which are known to be involved in the cortical response to pain, disappeared as in the control group. The beneficial use of vestibular stimulation in the reduction of pain and somatic delusion in a CPSP patient is now documented by behavioral and imaging data. This evidence can be applied to theoretical models of pain and body delusions.

  17. Caloric Vestibular Stimulation Reduces Pain and Somatoparaphrenia in a Severe Chronic Central Post-Stroke Pain Patient: A Case Study.

    Directory of Open Access Journals (Sweden)

    Grazia Fernanda Spitoni

    Full Text Available Central post-stroke pain is a neuropathic syndrome characterized by intolerable contralesional pain and, in rare cases, somatic delusions. To date, there is limited evidence for the effective treatments of this disease. Here we used caloric vestibular stimulation to reduce pain and somatoparaphrenia in a 57-year-old woman suffering from central post-stroke pain. Resting-state functional magnetic resonance imaging was used to assess the neurological effects of this treatment. Following vestibular stimulation we observed impressive improvements in motor skills, pain, and somatic delusions. In the functional connectivity study before the vestibular stimulation, we observed differences in the patient's left thalamus functional connectivity, with respect to the thalamus connectivity of a control group (N = 20, in the bilateral cingulate cortex and left insula. After the caloric stimulation, the left thalamus functional connectivity with these regions, which are known to be involved in the cortical response to pain, disappeared as in the control group. The beneficial use of vestibular stimulation in the reduction of pain and somatic delusion in a CPSP patient is now documented by behavioral and imaging data. This evidence can be applied to theoretical models of pain and body delusions.

  18. The neural mechanisms of pain-related affect and memory

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The pain experience includes a sensory-discriminative and an emotional-affective components. The affective dimension refers to the unpleasantness or aversion of sensation. The great progress at the genetic, molecular, cellular, and systemic levels on the study of the sensory dimension of pain has been made over past four decades. However, "to consider only the sensory features of pain, and ignore its motivational and affective properties, is to look at only part of the problem and not even the most important part of that". A line of clinic observations indicate that the patients with chronic pain suffer from much more affective disturbance than pain itself. Obviously,physiological arousal and hypervigilance to pain cause negative affect, such as anxiety, anger, worry, aversion, even tendency of suicide,these negative affective states in turn enhance pain sensation. Today, more and more attention has been paid to the study on mechanisms underlying affective dimension of pain. In order to deepen and expand our understanding of the nature of pain, this review summarizes the main progress and recent findings from our laboratory regarding affective component of pain in neuroanatomy, neurophysiology, and cell biochemistry.

  19. A randomized, placebo-controlled trial of levetiracetam in central pain in multiple sclerosis

    DEFF Research Database (Denmark)

    Falah, M; Madsen, C; Holbech, J V

    2012-01-01

    Levetiracetam is an anticonvulsant which is assumed to act by modulating neurotransmitter release via binding to the vesicle protein SV2A. This could have an impact on signalling in the pain pathway. The aim of this study was to test the analgesic effect of levetiracetam in central pain in multiple...... sclerosis. This was a randomized, double-blind, placebo-controlled, cross-over trial with levetiracetam 3000 mg/day versus placebo (6-week treatment periods). Patients with multiple sclerosis, symptoms and signs complying with central neuropathic pain and pain symptoms for more than 6 months, as well......-selected patients with central pain in multiple sclerosis, but an effect in subgroups with specific pain symptoms was indicated....

  20. Pain in the Blood? Envisioning Mechanism-Based Diagnoses and Biomarkers in Clinical Pain Medicine

    Directory of Open Access Journals (Sweden)

    Emmanuel Bäckryd

    2015-03-01

    Full Text Available Chronic pain is highly prevalent, and pain medicine lacks objective biomarkers to guide diagnosis and choice of treatment. The current U.S. “opioid epidemic” is a reminder of the paucity of effective and safe treatment options. Traditional pain diagnoses according to the International Classification of Diseases are often unspecific, and analgesics are often prescribed on a trial-and-error basis. In contrast to this current state of affairs, the vision of future mechanism-based diagnoses of chronic pain conditions is presented in this non-technical paper, focusing on the need for biomarkers and the theoretical complexity of the task. Pain is and will remain a subjective experience, and as such is not objectively measurable. Therefore, the concept of “noci-marker” is presented as an alternative to “pain biomarker”, the goal being to find objective, measurable correlates of the pathophysiological processes involved in different chronic pain conditions. This vision entails a call for more translational pain research in order to bridge the gap between clinical pain medicine and preclinical science.

  1. Usefulness of the Pain Tracking Technique in Acute Mechanical Low Back Pain

    Science.gov (United States)

    Bravo Acosta, Tania; Martín Cordero, Jorge E.; Hernández Tápanes, Solangel; Pedroso Morales, Isis; Fernández Cuesta, José Ignacio; Leyva Serrano, Maritza

    2015-01-01

    Objective. To evaluate the usefulness of the pain tracking technique in acute mechanical low back pain. Method. We performed an experimental prospective (longitudinal) explanatory study between January 2011 and September 2012. The sample was randomly divided into two groups. Patients were assessed at the start and end of the treatment using the visual analogue scale and the Waddell test. Treatment consisted in applying the pain tracking technique to the study group and interferential current therapy to the control group. At the end of treatment, cryotherapy was applied for 10 minutes. The Wilcoxon signed-rank test and the Mann Whitney test were used. They were performed with a predetermined significance level of p ≤ 0.05. Results. Pain was triggered by prolonged static posture and intense physical labor and intensified through trunk movements and when sitting and standing. The greatest relief was reported in lateral decubitus position and in William's position. The majority of the patients had contracture. Pain and disability were modified with the rehabilitation treatment in both groups. Conclusions. Both the pain tracking and interferential current techniques combined with cryotherapy are useful treatments for acute mechanical low back pain. The onset of analgesia is faster when using the pain tracking technique. PMID:26240758

  2. Usefulness of the Pain Tracking Technique in Acute Mechanical Low Back Pain

    Directory of Open Access Journals (Sweden)

    Tania Bravo Acosta

    2015-01-01

    Full Text Available Objective. To evaluate the usefulness of the pain tracking technique in acute mechanical low back pain. Method. We performed an experimental prospective (longitudinal explanatory study between January 2011 and September 2012. The sample was randomly divided into two groups. Patients were assessed at the start and end of the treatment using the visual analogue scale and the Waddell test. Treatment consisted in applying the pain tracking technique to the study group and interferential current therapy to the control group. At the end of treatment, cryotherapy was applied for 10 minutes. The Wilcoxon signed-rank test and the Mann Whitney test were used. They were performed with a predetermined significance level of p≤0.05. Results. Pain was triggered by prolonged static posture and intense physical labor and intensified through trunk movements and when sitting and standing. The greatest relief was reported in lateral decubitus position and in William’s position. The majority of the patients had contracture. Pain and disability were modified with the rehabilitation treatment in both groups. Conclusions. Both the pain tracking and interferential current techniques combined with cryotherapy are useful treatments for acute mechanical low back pain. The onset of analgesia is faster when using the pain tracking technique.

  3. Central adaptation of pain perception in response to rehabilitation of musculoskeletal pain

    DEFF Research Database (Denmark)

    Andersen, Lars L; Andersen, Christoffer H; Sundstrup, Emil;

    2012-01-01

    pain remains unclear. OBJECTIVE: To investigate the effect of neck/shoulder resistance training on pressure pain threshold (PPT) of the painful neck/shoulder muscles (upper trapezius) and a non-painful reference muscle of the leg (tibialis anterior) in adults with neck/shoulder pain. STUDY DESIGN...... of pain 186 days during the previous year, computer use 93% of work time) were randomly allocated to 10 weeks of specific resistance training for the neck/shoulder muscles for 2 or 12 minutes per day 5 times a week, or weekly information on general health (control group). Primary outcomes were changes...... in PPT of the painful neck/shoulder muscles (upper trapezius) and a distant non-painful reference muscle (tibialis anterior) at 10 weeks. RESULTS: PPT of both the trained painful trapezius and the non-trained reference muscle of the leg increased more in the training groups compared with the control...

  4. Belly dancer's myoclonus and chronic abdominal pain: pain-related dysinhibition of a spinal cord central pattern generator?

    Science.gov (United States)

    Tamburin, Stefano; Idone, Domenico; Zanette, Giampietro

    2007-07-01

    We report on a patient with segmental rhythmic myoclonus resembling belly dance. This patient developed the myoclonus in temporal and anatomical association with chronic abdominal pain. No structural or metabolic abnormalities were found. EMG recordings suggested the presence of a spinal cord central pattern generator (CPG). We hypothesize that pain-related spinal plasticity might have contributed to the hyperactivity of a spinal CPG, thus leading to the myoclonic jerks in our patient.

  5. Neurobiological Mechanism of Acupuncture for Relieving Visceral Pain of Gastrointestinal Origin

    Science.gov (United States)

    Zhao, Jimeng

    2017-01-01

    It is currently accepted that the neural transduction pathways of gastrointestinal (GI) visceral pain include the peripheral and central pathways. Existing research on the neurological mechanism of electroacupuncture (EA) in the treatment of GI visceral pain has primarily been concerned with the regulation of relevant transduction pathways. The generation of pain involves a series of processes, including energy transduction of stimulatory signals in the sensory nerve endings (signal transduction), subsequent conduction in primary afferent nerve fibers of dorsal root ganglia, and transmission to spinal dorsal horn neurons, the ascending transmission of sensory signals in the central nervous system, and the processing of sensory signals in the cerebral cortex. Numerous peripheral neurotransmitters, neuropeptides, and cytokines participate in the analgesic process of EA in visceral pain. Although EA has excellent efficacy in the treatment of GI visceral pain, the pathogenesis of the disease and the analgesic mechanism of the treatment have not been elucidated. In recent years, research has examined the pathogenesis of GI visceral pain and its influencing factors and has explored the neural transduction pathways of this disease. PMID:28243252

  6. Detection of central circuits implicated in the formation of novel pain memories

    Science.gov (United States)

    Upadhyay, Jaymin; Granitzka, Julia; Bauermann, Thomas; Baumgärtner, Ulf; Breimhorst, Markus; Treede, Rolf-Detlef; Birklein, Frank

    2016-01-01

    Being able to remember physically and emotionally painful events in one’s own past may shape behavior, and can create an aversion to a variety of situations. Pain imagination is a related process that may include recall of past experiences, in addition to production of sensory and emotional percepts without external stimuli. This study aimed to understand 1) the central nervous system processes that underlie pain imagination, 2) the retrieval of pain memories, and 3) to compare the latter with visual object memory. These goals were achieved by longitudinally investigating brain function with functional magnetic resonance imaging in a unique group of healthy volunteers who had never experienced tooth pain. In these subjects, we compared brain responses elicited during three experimental conditions in the following order: imagination of tooth pain (pain imagination), remembering one’s own house (object memory), and remembrance of tooth pain following an episode of induced acute tooth pain (pain memory). Key observations stemming from group-level conjunction analyses revealed common activation in the posterior parietal cortex for both pain imagination and pain memory, while object and pain memory each had strong activation predominantly within the middle frontal gyrus. When contrasting pain imagination and memory, significant activation differences were observed in subcortical structures (ie, parahippocampus − pain imagination > pain memory; midbrain − pain memory > pain imagination). Importantly, these findings were observed in the presence of consistent and reproducible psychophysical and behavioral measures that informed on the subjects’ ability to imagine novel and familiar thoughts, as well as the subjects’ pain perception.

  7. Central pain processing in chronic tension-type headache

    DEFF Research Database (Denmark)

    Lindelof, Kim; Ellrich, Jens; Jensen, Rigmor

    2009-01-01

    ) reflects neuronal excitability due to nociceptive input in the brainstem. The aim of this study was to investigate nociceptive processing at the level of the brainstem in an experimental pain model of CTTH symptoms. METHODS: The effect of conditioning pain, 5 min infusion of hypertonic saline into the neck...... muscles, was investigated in 20 patients with CTTH and 20 healthy controls. In addition, a pilot study with isotonic saline was performed with 5 subjects in each group. The BR was elicited by electrical stimuli with an intensity of four times the pain threshold, with a superficial concentric electrode. We...... measured the BR, sensibility to pressure and electrical pain scores before, during and 25 min after the saline infusion. RESULTS: The pain rating of the electrical stimuli and the pain score of the hypertonic saline infusion were significantly higher in CTTH patients than in healthy volunteers. The primary...

  8. Mechanisms of acupuncture analgesia for clinical and experimental pain.

    Science.gov (United States)

    Staud, Roland; Price, Donald D

    2006-05-01

    There is convincing evidence that acupuncture (AP) is effective for the treatment of postoperative and chemotherapy-induced nausea/vomiting, as well as postoperative dental pain. Less convincing data support AP's efficacy for chronic pain conditions, including headache, fibromyalgia and low back pain. There is no evidence that AP is effective in treating addiction, insomnia, obesity, asthma or stroke deficits. AP seems to be efficacious for alleviating experimental pain by increasing pain thresholds in human subjects and it appears to activate analgesic brain mechanisms through the release of neurohumoral factors, some of which can be inhibited by the opioid antagonist naloxone. In contrast to placebo analgesia, AP-related pain relief takes some time to develop and to resolve. Furthermore, repetitive use of AP analgesia can result in tolerance that demonstrates cross-tolerance with morphine. However, it appears that not all forms of AP are equally effective for providing analgesia. In particular, electro-AP seems to best deliver stimuli that activate powerful opioid and nonopioid analgesic mechanisms. Thus, future carefully controlled clinical trials using adequate electro-AP may be able to provide the necessary evidence for relevant analgesia in chronic pain conditions, such as headache, fibromyalgia, irritable bowel syndrome and low back pain.

  9. Pain in Breast Cancer Treatment: Aggravating Factors and Coping Mechanisms

    Directory of Open Access Journals (Sweden)

    Maria de Fatima Guerreiro Godoy

    2014-01-01

    Full Text Available The objective of this study was to evaluate pain in women with breast cancer-related lymphedema and the characteristics of aggravating factors and coping mechanisms. The study was conducted in the Clinica Godoy, São Jose do Rio Preto, with a group of 46 women who had undergone surgery for the treatment of breast cancer. The following variables were evaluated: type and length of surgery; number of radiotherapy and chemotherapy sessions; continued feeling of the removed breast (phantom limb, infection, intensity of pain, and factors that improve and worsen the pain. The percentage of events was used for statistical analysis. About half the participants (52.1% performed modified radical surgery, with 91.3% removing only one breast; 82.6% of the participants did not perform breast reconstruction surgery. Insignificant pain was reported by 32.60% of the women and 67.3% said they suffered pain; it was mild in 28.8% of the cases (scale 1–5, moderate in 34.8% (scale 6–9, and severe in 4.3%. The main mechanisms used to cope with pain were painkillers in 41.30% of participants, rest in 21.73%, religious ceremonies in 17.39%, and chatting with friends in 8.69%. In conclusion, many mastectomized patients with lymphedema complain of pain, but pain is often underrecognized and undertreated.

  10. Peripheral and central mechanisms of stress resilience

    Directory of Open Access Journals (Sweden)

    Madeline L. Pfau

    2015-01-01

    Full Text Available Viable new treatments for depression and anxiety have been slow to emerge, likely owing to the complex and incompletely understood etiology of these disorders. A budding area of research with great therapeutic promise involves the study of resilience, the adaptive maintenance of normal physiology and behavior despite exposure to marked psychological stress. This phenomenon, documented in both humans and animal models, involves coordinated biological mechanisms in numerous bodily systems, both peripheral and central. In this review, we provide an overview of resilience mechanisms throughout the body, discussing current research in animal models investigating the roles of the neuroendocrine, immune, and central nervous systems in behavioral resilience to stress.

  11. Effects of spinal manipulation in patients with mechanical neck pain

    Directory of Open Access Journals (Sweden)

    Diana Gregoletto

    2014-12-01

    Full Text Available Objective: To analyse changes in the range of motion (ROM and pain after spinal manipulation of the cervical spine and thoracic spine in subjects with mechanical neck pain. Methods : Spinal manipulations were performed in the cervical and thoracic spine with the Gonstead and Diversified DTV techniques. To assess cervical ROM an inclinometer was used. Cervical pain was assessed by Visual Analogue Scale (VAS. The participation of 73 patients was obtained. Ages ranged from 18 to 63 years, with an average of 42.27 years. The subjects of this study were characterized by having mechanical neck pain and restricted cervical ROM. Results: We observed a reduction in the intensity of pain perceived by patients and increased cervical ROM. There were significant differences between pre-treatment values (first visit and the fifth and tenth visits (p<0.01, and between the fifth and tenth visits (p<0.01 in all parameters except in the cervical extension of 70º. Conclusions: The results of this study suggest that spinal manipulation of the cervical and thoracic regions with the Gonstead and Diversified DTV techniques could subjectively reduce pain and produce considerable increase in cervical ROM in adults with mechanical neck pain.

  12. Chronic neuropathic pain: mechanisms, drug targets and measurement

    DEFF Research Database (Denmark)

    Finnerup, Nanna B; Sindrup, Søren H; Jensen, Troels S

    2007-01-01

    Neuropathic pain is common in many diseases or injuries of the peripheral or central nervous system, and has a substantial impact on quality of life and mood. Lesions of the nervous system may lead to potentially irreversible changes and imbalance between excitatory and inhibitory systems. Precli...

  13. Pathogenesis and mechanisms of pain in chronic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Dale E. Bockman

    2003-01-01

    The pathology of chronic pancreatitis is well known but the early events leading to the condition are less certain. Common characteristics of chronic pancreatitis, including fibrosis, chronic inflammation, and disappearance of parenchyma, usually are well established by the time tissue can be studied. Characteristics of acute pancreatitis may co-exist. Some experts assert that chronic pancreatitis begins with acute pancreatitis. Others consider that chronic pancreatitis develops first, and acute attacks occur on this background. The pain associated with chronic pancreatitis can be initiated through a variety of mechanisms. Increased pressure may distort nerves, affect blood flow, change pH, and cause retention of noxious substances, initiating action potentials. Tissue destruction and inflammation release biologically active materials capable of activating afferent nerves. Furthermore, inflammation damages nerves directly, triggering neuropathic pain. Understanding the neural pathways in the periphery and central nervous system that transmit impulses interpreted as pain should suggest the best methods for alleviating pancreatic pain. Pain may be transmitted through splanchnic, vagus, spinal, and phrenic peripheral nerves. It may be relayed through the dorsal columns of the spinal cord in addition to the spinothalamic tract. New methods of treating pancreatic pain therefore are possible.%虽然慢性胰腺炎的病理已经十分清楚,但其早期的致病机制尚不明确.慢性胰腺炎的一般特点为纤维化,慢性炎症和胰腺实质的消失,这些特征会随着疾病的发展而逐渐出现,同时还伴有急性胰腺炎的症状.一些专家认为慢性胰腺炎继发于急性胰腺炎.另一些则认为慢性胰腺炎首先发生,急性胰腺炎则在此基础上发生.慢性胰腺炎所引起的疼痛可通过许多机制发生.增高的胰腺压力可干扰神经,影响血流,改变pH值,并引起有毒物质的潴留,激活动作电位.组织的

  14. Forebrain Mechanisms of Nociception and Pain: Analysis through Imaging

    Science.gov (United States)

    Casey, Kenneth L.

    1999-07-01

    Pain is a unified experience composed of interacting discriminative, affective-motivational, and cognitive components, each of which is mediated and modulated through forebrain mechanisms acting at spinal, brainstem, and cerebral levels. The size of the human forebrain in relation to the spinal cord gives anatomical emphasis to forebrain control over nociceptive processing. Human forebrain pathology can cause pain without the activation of nociceptors. Functional imaging of the normal human brain with positron emission tomography (PET) shows synaptically induced increases in regional cerebral blood flow (rCBF) in several regions specifically during pain. We have examined the variables of gender, type of noxious stimulus, and the origin of nociceptive input as potential determinants of the pattern and intensity of rCBF responses. The structures most consistently activated across genders and during contact heat pain, cold pain, cutaneous laser pain or intramuscular pain were the contralateral insula and anterior cingulate cortex, the bilateral thalamus and premotor cortex, and the cerebellar vermis. These regions are commonly activated in PET studies of pain conducted by other investigators, and the intensity of the brain rCBF response correlates parametrically with perceived pain intensity. To complement the human studies, we developed an animal model for investigating stimulus-induced rCBF responses in the rat. In accord with behavioral measures and the results of human PET, there is a progressive and selective activation of somatosensory and limbic system structures in the brain and brainstem following the subcutaneous injection of formalin. The animal model and human PET studies should be mutually reinforcing and thus facilitate progress in understanding forebrain mechanisms of normal and pathological pain.

  15. Assessing the risk of central post-stroke pain of thalamic origin by lesion mapping.

    Science.gov (United States)

    Sprenger, Till; Seifert, Christian L; Valet, Michael; Andreou, Anna P; Foerschler, Annette; Zimmer, Claus; Collins, D Louis; Goadsby, Peter J; Tölle, Thomas R; Chakravarty, M Mallar

    2012-08-01

    Central post-stroke pain of thalamic origin is an extremely distressing and often refractory disorder. There are no well-established predictors for pain development after thalamic stroke, and the role of different thalamic nuclei is unclear. Here, we used structural magnetic resonance imaging to identify the thalamic nuclei, specifically implicated in the generation of central post-stroke pain of thalamic origin. Lesions of 10 patients with central post-stroke pain of thalamic origin and 10 control patients with thalamic strokes without pain were identified as volumes of interest on magnetic resonance imaging data. Non-linear deformations were estimated to match each image with a high-resolution template and were applied to each volume of interest. By using a digital atlas of the thalamus, we elucidated the involvement of different nuclei with respect to each lesion. Patient and control volumes of interest were summed separately to identify unique areas of involvement. Voxelwise odds ratio maps were calculated to localize the anatomical site where lesions put patients at risk of developing central post-stroke pain of thalamic origin. In the patients with pain, mainly lateral and posterior thalamic nuclei were affected, whereas a more anterior-medial lesion pattern was evident in the controls. The lesions of 9 of 10 pain patients overlapped at the border of the ventral posterior nucleus and the pulvinar, coinciding with the ventrocaudalis portae nucleus. The lesions of this area showed an odds ratio of 81 in favour of developing thalamic pain. The high odds ratio at the ventral posterior nucleus-pulvinar border zone indicates that this area is crucial in the pathogenesis of thalamic pain and demonstrates the feasibility of identifying patients at risk of developing central post-stroke pain of thalamic origin early after thalamic insults. This provides a basis for pre-emptive treatment studies.

  16. Central Sensitization and Perceived Indoor Climate among Workers with Chronic Upper-Limb Pain

    DEFF Research Database (Denmark)

    Sundstrup, Emil; Jakobsen, Markus D; Brandt, Mikkel;

    2015-01-01

    threshold (PPT) was measured in muscles of the arm, shoulder, and lower leg. Cross-sectional associations were determined using general linear models controlled for age, smoking, and job position. The number of indoor climate complaints was twice as high among workers with chronic pain compared with pain...... not account for musculoskeletal pain in questionnaire assessment of indoor climate may be biased. Central sensitization likely explains the present findings....

  17. Computational Modeling and Analysis of Mechanically Painful Stimulations

    DEFF Research Database (Denmark)

    Manafi Khanian, Bahram

    to expand the current knowledge on the mechanical influences of cuff algometry on deep-tissue nociceptors. Additionally, this is one of the pioneering projects utilizing the finite element simulation as a computationally reliable method of modelling in pain research field. The present findings are highly...... relevant to biomechanical studies for defining a valid methodology to appropriately activate deep-tissue nociceptors and hence to develop biomedical devices used for pain sensitivity assessment....

  18. Musculoskeletal pain among postmenopausal women in Nigeria: Association with overall and central obesity

    Directory of Open Access Journals (Sweden)

    Omoyemi O. Ogwumike, PhD

    2016-06-01

    Conclusion: Lower extremity and back pain symptoms were the most prevalent. For overall and central obesity directly associated with MSP, WHtR seemed the best obesity screening tool for MSP in postmenopausal women.

  19. Central post-stroke pain%卒中后中枢性疼痛

    Institute of Scientific and Technical Information of China (English)

    宋海庆; 武剑

    2015-01-01

    Central post-stroke pain refers to pain resulting from a primary lesion or dysfunction of the central nervous system after a stroke.The prevalence of central post-stroke pain varies from 8% to 46%.This article reviews the definition,epidemiology,pathophysiology,clinical features,and treatment of central post-stroke pain.%卒中后中枢性疼痛是指卒中后因中枢神经系统原发病灶或功能障碍引起的疼痛,患病率为8%~35%.文章对卒中后中枢性疼痛的定义、流行病学、病理生理学机制、临床特征、诊断和治疗等进行了综述.

  20. Analgesic effect of transcranial direct current stimulation on central post-stroke pain.

    Science.gov (United States)

    Bae, Sea-Hyun; Kim, Gi-Do; Kim, Kyung-Yoon

    2014-01-01

    Pain that occurs after a stroke lowers the quality of life. Such post-stroke pain is caused in part by the brain lesion itself, called central post-stroke pain. We investigated the analgesic effects of transcranial direct current stimulation (tDCS) in stroke patients through quantitative sensory testing. Fourteen participants with central post-stroke pain (7 female and 7 male subjects) were recruited and were allocated to either tDCS (n = 7) or sham-tDCS (n = 7) group. Their ages ranged from 45 to 55 years. tDCS was administered for 20 min at a 2-mA current intensity, with anodal stimulations were performed at primary motor cortex. The sham-tDCS group was stimulated 30-second current carrying time. Both group interventions were given for 3 days per week, for a period of 3 weeks. Subjective pain was measured using the visual analogue scale (VAS) of 0 to 10. Sensations of cold and warmth, and pain from cold and heat were quantified to examine analgesic effects. The sham-tDCS group showed no statistically significant differences in time. In contrast, tDCS group showed decreased VAS scores and skin temperature (p pain from cold increased (p pain from heat decreased (p central post-stroke pain.

  1. Meta-analysis of placebo responses in central neuropathic pain: impact of subject, study, and pain characteristics.

    Science.gov (United States)

    Cragg, Jacquelyn J; Warner, Freda M; Finnerup, Nanna Brix; Jensen, Mark P; Mercier, Catherine; Richards, John Scott; Wrigley, Paul; Soler, Dolors; Kramer, John L K

    2016-03-01

    The placebo response is a complex construct related to psychobiological effects, as well as natural history and regression to the mean. Moreover, patient and study design characteristics have also been proposed as significantly affecting placebo responses. The aim of the current investigation was to identify factors that contribute to variable placebo responses in clinical trials involving individuals with central neuropathic pain. To this end, we performed a systematic review and meta-analysis of placebo-controlled trials examining pharmacological and noninvasive brain stimulation interventions for central neuropathic pain. Study design, subject characteristics, and pain ratings for the placebo group were extracted from each trial. Pooling of results and identification of moderating factors were carried out using random effects meta-analysis and meta-regression techniques. A total of 39 published trials met the inclusion criteria (spinal cord injury, n = 26; stroke, n = 6; multiple sclerosis, n = 7). No significant publication bias was detected. Overall, there was a significant effect for placebo to reduce central pain (-0.64, CI: -0.83 to -0.45). Smaller placebo responses were associated with crossover-design studies, longer pain duration, and greater between-subject baseline pain variability. There were no significant effects for neurological condition (stroke vs multiple sclerosis vs spinal cord injury) or the type of intervention (eg, pharmacological vs noninvasive brain stimulation). In a planned subanalysis, the severity of damage in the spinal cord also had no significant effect on the placebo response. Further study is warranted to identify factors that may explain the impact of pain duration on the placebo response at the individual subject level.

  2. Bilateral central pain sensitization in rats following a unilateral thalamic lesion may be treated with high doses of ketamine

    Science.gov (United States)

    2013-01-01

    Background Central post-stroke pain is a neuropathic pain condition caused by a vascular lesion, of either ischemic or hemorrhagic origin, in the central nervous system and more precisely involving the spinothalamocortical pathway responsible for the transmission of painful sensations. Few animal models have been developed to study this problem. The objectives of this study were to evaluate different modalities of pain in a central neuropathic pain rat model and to assess the effects of ketamine administered at different doses. Animals were evaluated on the rotarod, Hargreaves, Von Frey and acetone tests. A very small hemorrhage was created by injecting a collagenase solution in the right ventral posterolateral thalamic nucleus. Following the establishment of the neuropathy, ketamine was evaluated as a therapeutic drug for this condition. Results Histopathological observations showed a well localized lesion with neuronal necrosis and astrocytosis following the collagenase injection that was localized within the VPL. No significant change in motor coordination was observed following surgery in either the saline or collagensae groups. In the collagenase group, a significant decrease in mechanical allodynia threshold was observed. A sporadic and transient cold allodynia was also noted. No thermal hyperalgesia was seen following the collagenase injection. Ketamine was then tested as a potential therapeutic drug. A significant decrease in motor coordination was seen only following the administration of 25 mg/kg of ketamine in both groups. An alleviation of mechanical allodynia was achieved only with the high ketamine dose. The minimal effective ketamine serum concentration (150 ng/mL) was only achieved in animals that received 25 mg/kg. Conclusions An intrathalamic hemorrhage induced a bilateral mechanical allodynia in rats. Cold hyperalgesia was observed in 60% of these animals. Mechanical allodynia was alleviated with high doses of ketamine which corresponded

  3. [Mechanisms by which acute orofacial pain becomes chronic].

    Science.gov (United States)

    Cahana, A; Forster, A

    2006-06-01

    Pain is a complex, multidimensional experience encompassing sensory-discriminative, cognitive, emotional and motivational dimensions. These dimensions in the orofacial region have particular expression since the face and mouth have special biological, emotional and psychological meaning to each individual. Orofacial pain is frequent. Epidemiological studies reveal a high prevalence of severe pain in syndromes such as temporomandibular disorders (TMD), burning mouth syndrome and toothaches, as well as an important role of psychosocial influences, contributing to the persistence of these syndromes. Many of the difficulties experienced by clinicians with the diagnosis and management of acute and chronic orofacial pain stem from a lack of recognition and understanding of these complex conditions, the various intricate bio-psycho-social interactions and the neurobiology behind the chronicisation of acute pain. This text strives to review the important advances and insights into the peripheral processes by which noxious stimuli activates or modulates nociceptive afferent input into the brainstem, the neural pathways in the brainstem and higher levels of the trigeminal (V) somatosensory system and the mechanisms involved in the plasticity of nociceptive transmission. We shall link this knowledge to clinical correlates and suggest a therapeutic approach in acute orofacial pain, in the attempt to avoid the development of chronic pain.

  4. Conceptual Conditioning: Mechanisms Mediating Conditioning Effects on Pain.

    Science.gov (United States)

    Jepma, Marieke; Wager, Tor D

    2015-11-01

    Classical conditioning can profoundly modify subsequent pain responses, but the mechanisms that drive this effect are unresolved. In pain-conditioning studies, cues are typically conditioned to primary aversive reinforcers; hence, subsequent pain modulation could reflect learned precognitive associations (i.e., those involving neural plasticity independent of expectations and other forms of conceptual thought) or conceptual expectancies. We isolated conceptual contributions using a thermal pain-conditioning procedure in which different conditioned stimulus (CS) cues were repeatedly paired with symbolic representations of high and low noxious heat. In a subsequent test phase, identical noxious stimuli evoked larger skin conductance responses (SCRs) and pain ratings when preceded by CS cues associated with high temperature than by those associated with low temperature. These effects were mediated by participants' self-reported expectancies. CS cues associated with high temperature also evoked larger anticipatory SCRs than did CS cues associated with low temperature, but larger anticipatory SCRs predicted smaller subsequent heat-evoked SCRs. These results provide novel evidence that conditioned modulation of pain physiology can be acquired through purely conceptual processes, and that self-reported expectancies and physiological threat responses have opposing effects on pain.

  5. Neuropathic Pain Following Spinal Cord Injury: Mechanism, Assessment and Treatment

    Directory of Open Access Journals (Sweden)

    Gul Mete Civelek

    2016-04-01

    Full Text Available Spinal cord injury (SCI is a devastating disease which may cause physical, psychological and social dysfunction. Neuropathic pain (NP after SCI is common, can be seen in varying degrees and is one of the most difficultly treated problems developing after SCI. With the addition of the NP to loss of function after SCI, sleep patterns, moods and daily activities of patients are adversely affected. In order to treat pain effectively, classification of pain after SCI must be done carefully and correctly. According to classification of International Pain Study Group, pain after SCI is divided into two main groups as nociceptive and neuropathic pain. Neuropathic pain is defined as %u201Cpain occuring as a direct result of a disease or lesion directly affecting somato-sensorial system%u201D. NP after SCI can be classified according to anatomical region (above the level of lesion, at the level of lesion, below the level of lesion. Treatment of NP after SCI is often challenging and receiving response to treatment may take long time. Therefore, treatment of NP after SCI should be multifactorial. Treatment options include pharmochologic treatment, application of transcutanous electrical nerve stimulation, psychiatric treatment approaches, and surgical approaches in selected cases. In pharmachologic treatment, first line agents are tricyclic antidepresants, pregabalin and gabapentin. In this review, mechanisms and assessment and treatment of NP after SCI is discussed with the guide of current literature.

  6. The Central Mystery of Quantum Mechanics

    OpenAIRE

    Ghose, Partha

    2009-01-01

    A critical re-examination of the double-slit experiment and its variants is presented to clarify the nature of what Feynmann called the ``central mystery'' and the ``only mystery'' of quantum mechanics, leading to an interpretation of complementarity in which a `wave {\\em and} particle' description rather than a `wave {\\em or} particle' description is valid for the {\\em same} experimental set up, with the wave culminating in the particle sequentially in time. This interpretation is different ...

  7. Assessment of pressure-pain thresholds and central sensitization of pain in lateral epicondylalgia

    DEFF Research Database (Denmark)

    Jespersen, Anders; Amris, Kirstine; Graven-Nielsen, Thomas

    2013-01-01

    pressure stimulation at intensity relative to the individual pain threshold, the pain intensity was continuously recorded using an electronic visual analogue scale (VAS), and from this the degree of temporal summation was estimated. For LE, a Doppler ultrasound examination of the elbow was made to identify...

  8. Probable Mechanisms of Needling Therapies for Myofascial Pain Control

    Directory of Open Access Journals (Sweden)

    Li-Wei Chou

    2012-01-01

    Full Text Available Myofascial pain syndrome (MPS has been defined as a regional pain syndrome characterized by muscle pain caused by myofascial trigger points (MTrPs clinically. MTrP is defined as the hyperirritable spot in a palpable taut band of skeletal muscle fibers. Appropriate treatment to MTrPs can effectively relieve the clinical pain of MPS. Needling therapies, such as MTrP injection, dry needling, or acupuncture (AcP can effectively eliminate pain immediately. AcP is probably the first reported technique in treating MPS patients with dry needling based on the Traditional Chinese Medicine (TCM theory. The possible mechanism of AcP analgesia were studied and published in recent decades. The analgesic effect of AcP is hypothesized to be related to immune, hormonal, and nervous systems. Compared to slow-acting hormonal system, nervous system acts in a faster manner. Given these complexities, AcP analgesia cannot be explained by any single mechanism. There are several principles for selection of acupoints based on the TCM principles: “Ah-Shi” point, proximal or remote acupoints on the meridian, and extra-meridian acupoints. Correlations between acupoints and MTrPs are discussed. Some clinical and animal studies of remote AcP for MTrPs and the possible mechanisms of remote effectiveness are reviewed and discussed.

  9. Supraspinal brain-derived neurotrophic factor signaling: a novel mechanism for descending pain facilitation.

    Science.gov (United States)

    Guo, Wei; Robbins, Meredith T; Wei, Feng; Zou, Shiping; Dubner, Ronald; Ren, Ke

    2006-01-04

    In the adult mammalian brain, brain-derived neurotrophic factor (BDNF) is critically involved in long-term synaptic plasticity. Here, we show that supraspinal BDNF-tyrosine kinase receptor B (TrkB) signaling contributes to pain facilitation. We show that BDNF-containing neurons in the periaqueductal gray (PAG), the central structure for pain modulation, project to and release BDNF in the rostral ventromedial medulla (RVM), a relay between the PAG and spinal cord. BDNF in PAG and TrkB phosphorylation in RVM neurons are upregulated after inflammation. Intra-RVM sequestration of BDNF and knockdown of TrkB by RNA interference attenuate inflammatory pain. Microinjection of BDNF (10-100 fmol) into the RVM facilitates nociception, which is dependent on NMDA receptors (NMDARs). In vitro studies with RVM slices show that BDNF induces tyrosine phosphorylation of the NMDAR NR2A subunit in RVM via a signal transduction cascade involving IP(3), PKC, and Src. The supraspinal BDNF-TrkB signaling represents a previously unknown mechanism underlying the development of persistent pain. Our findings also caution that application of BDNF for recovery from CNS disorders could lead to undesirable central pain.

  10. Central N/OFQ-NOP Receptor System in Pain Modulation.

    Science.gov (United States)

    Kiguchi, Norikazu; Ding, Huiping; Ko, Mei-Chuan

    2016-01-01

    Two decades have passed since the peptide, nociceptin/orphanin FQ (N/OFQ), and its cognate (NOP) receptor were discovered. Although NOP receptor activation causes a similar pattern of intracellular actions as mu-opioid (MOP) receptors, NOP receptor-mediated pain modulation in rodents are more complicated than MOP receptor activation. This review highlights the functional evidence of spinal, supraspinal, and systemic actions of NOP receptor agonists for regulating pain. In rodents, effects of the N/OFQ-NOP receptor system in spinal and supraspinal sites for modulating pain are bidirectional depending on the doses, assays, and pain modalities. The net effect of systemically administered NOP receptor agonists may depend on relative contribution of spinal and supraspinal actions of the N/OFQ-NOP receptor signaling in rodents under different pain states. In stark contrast, NOP receptor agonists produce only antinociception and antihypersensitivity in spinal and supraspinal regions of nonhuman primates regardless of doses and assays. More importantly, NOP receptor agonists and a few bifunctional NOP/MOP receptor agonists do not exhibit reinforcing effects (abuse liability), respiratory depression, itch pruritus, nor do they delay the gastrointestinal transit function (constipation) in nonhuman primates. Depending upon their intrinsic efficacies for activating NOP and MOP receptors, bifunctional NOP/MOP receptor agonists warrant additional investigation in primates regarding their side effect profiles. Nevertheless, NOP receptor-related agonists display a much wider therapeutic window as compared to that of MOP receptor agonists in primates. Both selective NOP receptor agonists and bifunctional NOP/MOP receptor agonists hold great potential as effective and safe analgesics without typical opioid-associated side effects in humans.

  11. An Induced Hematoma in Caudoputamen Nuclei in Rats Causes Central Pain when the Thalamus is also Implicated and the Central Sensitization is Reversed with Gabapentin

    Directory of Open Access Journals (Sweden)

    P. P. Lema

    2012-01-01

    Full Text Available Problem statement: The objective of this study was to evaluate pain sensitisation in rats following the induction of an intracerebral hemorrhage by injecting a collagenase solution in the caudoputamen nucleus of the right basal ganglia and to evaluate gabapentin as an analgesic for central pain. Approach: Thirty male Sprague-Dawley rats weighing between 175-300 g were used. In a first experiment, 3 groups of 6 animals were used to evaluate pain threshold using the Hargreaves test (thermal sensitivity only. Following 3 days of behavioral testing (baseline values, animals in each group were injected intracerebrally either with 0.5, 1 or 2 μL of a collagenase solution (0.5 U 2 μL-1 Type VII collagenase inducing a hematoma in the right caudoputamen nucleus and/or thalamus. They were then tested for the next 9 consecutive days. In a second experiment, gabapentin was evaluated for the reversal of thermal hyperalgesia and mechanical allodynia (using von Frey filaments following the intracerebral injection of 3 μL of the collagenase solution. Results: No pain-related behavioral changes were observed following injections with 0.5 and 1 μL of the collagenase solution. However with 2 μL, reaction times were significantly faster on days 3-7 in the right and left hind paws compared to baseline values. The lesion was localized only in the caudoputamen nucleus for animals receiving 0.5 and 1 μL of collagenase whereas lesions extended in the ipsilateral thalamic nuclei (lateral-dorsal and lateral-posterior nuclei for animals receiving 2 μL of collagenase. Gabapentin reversed mechanical allodynia and thermal hyperalgesia in animals with caudoputamen and thalamic lesions. Conclusion: These preliminary results suggest that central pain was induced in rats with a collagenase-induced intracerebral hemorrhage localized in the thalamus and that mechanical allodynia and thermal hyperalgesia were reduced with gabapentin treatment.

  12. Alcohol consumption enhances antiretroviral painful peripheral neuropathy by mitochondrial mechanisms.

    Science.gov (United States)

    Ferrari, Luiz F; Levine, Jon D

    2010-09-01

    A major dose-limiting side effect of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) chemotherapies, such as the nucleoside reverse transcriptase inhibitors (NRTIs), is a small-fiber painful peripheral neuropathy, mediated by its mitochondrial toxicity. Co-morbid conditions may also contribute to this dose-limiting effect of HIV/AIDS treatment. Alcohol abuse, which alone also produces painful neuropathy, is one of the most important co-morbid risk factors for peripheral neuropathy in patients with HIV/AIDS. Despite the prevalence of this problem and its serious impact on the quality of life and continued therapy in HIV/AIDS patients, the mechanisms by which alcohol abuse exacerbates highly active antiretroviral therapy (HAART)-induced neuropathic pain has not been demonstrated. In this study, performed in rats, we investigated the cellular mechanism by which consumed alcohol impacts antiretroviral-induced neuropathic pain. NRTI 2',3'-dideoxycytidine (ddC; 50 mg/kg) neuropathy was mitochondrial-dependent and PKCε-independent, and alcohol-induced painful neuropathy was PKCε-dependent and mitochondrial-independent. At low doses, ddC (5 mg/kg) and alcohol (6.5% ethanol diet for 1 week), which alone do not affect nociception, together produce profound mechanical hyperalgesia. This hyperalgesia is mitochondrial-dependent but PKCε-independent. These experiments, which provide the first model for studying the impact of co-morbidity in painful neuropathy, support the clinical impression that alcohol consumption enhances HIV/AIDS therapy neuropathy, and provide evidence for a role of mitochondrial mechanisms underlying this interaction.

  13. Molecular mechanisms underlying the effects of acupuncture on neuropathic pain**

    Institute of Scientific and Technical Information of China (English)

    Ziyong Ju; Huashun Cui; Xiaohui Guo; Huayuan Yang; Jinsen He; Ke Wang

    2013-01-01

    Acupuncture has been used to treat neuropathic pain for a long time, but its mechanisms of action remain unknown. In this study, we observed the effects of electroacupuncture and manual acu-puncture on neuropathic pain and on ephrin-B/EphB signaling in rats models of chronic constriction injury-induced neuropathic pain. The results showed that manual acupuncture and elec-puncture significantly reduced mechanical hypersensitivity fol owing chronic constriction injury, es-pecial y electroacupuncture treatment. Real-time PCR results revealed that ephrin-B1/B3 and EphB1/B2 mRNA expression levels were significantly increased in the spinal dorsal horns of chronic constriction injury rats. Electroacupuncture and manual acupuncture suppressed the high sion of ephrin-B1 mRNA, and elevated EphB3/B4 mRNA expression. Electroacupuncture signifi-cantly enhanced the mRNA expression of ephrin-B3 and EphB3/B6 in the dorsal horns of neuro-pathic pain rats. Western blot results revealed that electroacupuncture in particular, and manual acupuncture, significantly up-regulated ephrin-B3 protein levels in rat spinal dorsal horns. The re-sults of this study suggest that acupuncture could activate ephrin-B/EphB signaling in neuropathic pain rats and improve neurological function.

  14. Assessment of Mechanical Pain Thresholds in the Orofacial Region

    DEFF Research Database (Denmark)

    Suzuki, Kayo; Baad-Hansen, Lene; Pigg, Maria;

    2016-01-01

    AIMS: To compare mechanical pain thresholds (MPTs) in the orofacial region assessed with two different approaches: with an electronic von Frey (EvF) device and with custom-made weighted pinprick stimulators. The test-retest reliability, variability of MPTs, and time duration of each test were also...

  15. A central neuropathic pain model by DSP-4 induced lesion of noradrenergic neurons: preliminary report.

    Science.gov (United States)

    Kudo, Takashi; Kushikata, Tetsuya; Kudo, Mihoko; Kudo, Tsuyoshi; Hirota, Kazuyoshi

    2010-09-06

    Neuropathic pain models are classified as central and peripheral pain models. Although various peripheral neuropathic pain models are established, central pain models are based only on spinal cord injury. DSP-4 is a competitive inhibitor of norepinephrine uptake that selectively degenerates the locus coeruleus (LC)-noradrenergic neurons projection to the cerebral cortex and hippocampus. In the present study, we have tested whether lesion of LC-noradrenergic neurons by ip DSP-4 (0, 10, 30, 50 mg/kg, n=7 each) could provide a new central neuropathic pain model in rats using a hot-plate and tail-flick tests. DSP-4 significantly reduced the hot-plate latency and norepinephrine contents especially in the coerulean regions. However, DSP-4 did not change tail-flick latency. There are significant correlations of the latency in the hot-plate test with norepinephrine contents in the cerebral cortex (r=0.432, p=0.022), the hippocampus (r=0.465, p=0.013) and the pons (r=0.400, p=0.035) but not with those in the hypothalamus and the spinal cord. As response to hot-plate and tail-flick implies supra-spinal process and spinal reflex, respectively, central neuropathic pain may be facilitated by DSP-4 depleting LC-noradrenergic neurons although the present data are preliminary.

  16. Antinociception of ciproxifan in mice and its central mechanisms

    Institute of Scientific and Technical Information of China (English)

    Hui-jingWANG; Zhi-liHUANG; Ying-qingLU; RongYU; Qin-yanGONG; Nian-ciSHI; Ming-huiYAO

    2005-01-01

    AIM To investigate the effects of ciproxifan (CPF), an H3 receptor antagnist, on modulation of pain transmission in mice and its central mechanism. METHODS The antinociceptive effect of CPF was observed in three hyperalgesic models of mice (hot plate test, writhing test and formalin test). At the same time, α-fluoromethylhistidine (α-FMH), a specific inhibitor of histidine decarboxylase(HDC), was used to determine whether histamine participate in this process. After formalin test, the levels of nitric oxide (NO) and prostaglandin E2 (PGE2) in brain, spinal and serum were assessed. Furthermore, the activation of neuronal nitric oxide synthase (nNOS) in brain and spinal cord was observed by immunohistology and Western blot in formalin test. RESULTS CPF produced antinociceptive effect inall of the three hyperalgesic models.

  17. Effectiveness of low-dose pregabalin in three patients with Lewy body disease and central neuropathic pain.

    Science.gov (United States)

    Ukai, Katsuyuki; Fujishiro, Hiroshige; Ozaki, Norio

    2017-03-01

    Many patients with Lewy body disease complain of pain, and their pain may be associated with this disease. Recently, pain has become a focus of attention in Parkinson's disease, but there is little information regarding pain in patients who have dementia with Lewy bodies. We used pregabalin to treat three Lewy body disease patients with chronic pain that may have been related to degeneration of central neurons. All three patients responded well to pregabalin at 25-50 mg/day. To our knowledge, there have been no previous reports of pregabalin showing efficacy for central neuropathic pain in Parkinson's disease or Lewy body disease.

  18. Understanding the pelvic pain mechanism is key to find an adequate therapeutic approach.

    Science.gov (United States)

    Van Kerrebroeck, Philip

    2016-06-25

    Pain is a natural mechanism to actual or potential tissue damage and involves both a sensory and an emotional experience. In chronic pelvic pain, localisation of pain can be widespread and can cause considerable distress. A multidisciplinary approach is needed in order to fully understand the pelvic pain mechanism and to identify an adequate therapeutic approach.

  19. Pregabalin and placebo responders show different effects on central pain processing in chronic pancreatitis patients

    NARCIS (Netherlands)

    Bouwense, S.A.; Olesen, S.S.; Drewes, A.M.; Goor, H. van; Wilder-Smith, O.H.G.

    2015-01-01

    BACKGROUND: Pain control in chronic pancreatitis is a major challenge; the mechanisms behind analgesic treatment are poorly understood. This study aims to investigate the differences in pain sensitivity and modulation in chronic pancreatitis patients, based on their clinical response (responders vs

  20. Mechanisms-based classifications of musculoskeletal pain: part 3 of 3: symptoms and signs of nociceptive pain in patients with low back (± leg) pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-08-01

    As a mechanisms-based classification of pain \\'nociceptive pain\\' (NP) refers to pain attributable to the activation of the peripheral receptive terminals of primary afferent neurones in response to noxious chemical, mechanical or thermal stimuli. The symptoms and signs associated with clinical classifications of NP have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of NP in patients with low back (± leg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (± leg) pain were assessed using a standardised assessment protocol after which their pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist indicating the presence\\/absence of various symptoms and signs. A regression analysis identified a cluster of seven clinical criteria predictive of NP, including: \\'Pain localised to the area of injury\\/dysfunction\\

  1. Time perception mechanisms at central nervous system

    Directory of Open Access Journals (Sweden)

    Rhailana Fontes

    2016-04-01

    Full Text Available The five senses have specific ways to receive environmental information and lead to central nervous system. The perception of time is the sum of stimuli associated with cognitive processes and environmental changes. Thus, the perception of time requires a complex neural mechanism and may be changed by emotional state, level of attention, memory and diseases. Despite this knowledge, the neural mechanisms of time perception are not yet fully understood. The objective is to relate the mechanisms involved the neurofunctional aspects, theories, executive functions and pathologies that contribute the understanding of temporal perception. Articles form 1980 to 2015 were searched by using the key themes: neuroanatomy, neurophysiology, theories, time cells, memory, schizophrenia, depression, attention-deficit hyperactivity disorder and Parkinson’s disease combined with the term perception of time. We evaluated 158 articles within the inclusion criteria for the purpose of the study. We conclude that research about the holdings of the frontal cortex, parietal, basal ganglia, cerebellum and hippocampus have provided advances in the understanding of the regions related to the perception of time. In neurological and psychiatric disorders, the understanding of time depends on the severity of the diseases and the type of tasks.

  2. Time Perception Mechanisms at Central Nervous System

    Science.gov (United States)

    Fontes, Rhailana; Ribeiro, Jéssica; Gupta, Daya S.; Machado, Dionis; Lopes-Júnior, Fernando; Magalhães, Francisco; Bastos, Victor Hugo; Rocha, Kaline; Marinho, Victor; Lima, Gildário; Velasques, Bruna; Ribeiro, Pedro; Orsini, Marco; Pessoa, Bruno; Leite, Marco Antonio Araujo; Teixeira, Silmar

    2016-01-01

    The five senses have specific ways to receive environmental information and lead to central nervous system. The perception of time is the sum of stimuli associated with cognitive processes and environmental changes. Thus, the perception of time requires a complex neural mechanism and may be changed by emotional state, level of attention, memory and diseases. Despite this knowledge, the neural mechanisms of time perception are not yet fully understood. The objective is to relate the mechanisms involved the neurofunctional aspects, theories, executive functions and pathologies that contribute the understanding of temporal perception. Articles form 1980 to 2015 were searched by using the key themes: neuroanatomy, neurophysiology, theories, time cells, memory, schizophrenia, depression, attention-deficit hyperactivity disorder and Parkinson’s disease combined with the term perception of time. We evaluated 158 articles within the inclusion criteria for the purpose of the study. We conclude that research about the holdings of the frontal cortex, parietal, basal ganglia, cerebellum and hippocampus have provided advances in the understanding of the regions related to the perception of time. In neurological and psychiatric disorders, the understanding of time depends on the severity of the diseases and the type of tasks. PMID:27127597

  3. Transcutaneous electrical nerve stimulation reduces pain, fatigue and hyperalgesia while restoring central inhibition in primary fibromyalgia.

    Science.gov (United States)

    Dailey, Dana L; Rakel, Barbara A; Vance, Carol G T; Liebano, Richard E; Amrit, Anand S; Bush, Heather M; Lee, Kyoung S; Lee, Jennifer E; Sluka, Kathleen A

    2013-11-01

    Because transcutaneous electrical nerve stimulation (TENS) works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double-blinded randomized, placebo-controlled cross-over design to test the effects of a single treatment of TENS with people with fibromyalgia. Three treatments were assessed in random order: active TENS, placebo TENS and no TENS. The following measures were assessed before and after each TENS treatment: pain and fatigue at rest and in movement; pressure pain thresholds, 6-m walk test, range of motion; 5-time sit-to-stand test, and single-leg stance. Conditioned pain modulation was completed at the end of testing. There was a significant decrease in pain and fatigue with movement for active TENS compared to placebo and no TENS. Pressure pain thresholds increased at the site of TENS (spine) and outside the site of TENS (leg) when compared to placebo TENS or no TENS. During active TENS, conditioned pain modulation was significantly stronger compared to placebo TENS and no TENS. No changes in functional tasks were observed with TENS. Thus, the current study suggests TENS has short-term efficacy in relieving symptoms of fibromyalgia while the stimulator is active. Future clinical trials should examine the effects of repeated daily delivery of TENS, similar to the way in which TENS is used clinically on pain, fatigue, function, and quality of life in individuals with fibromyalgia.

  4. Population-based study of central post-stroke pain in Rimini district, Italy

    Directory of Open Access Journals (Sweden)

    Raffaeli W

    2013-09-01

    Full Text Available William Raffaeli,1 Cristina E Minella,2 Francesco Magnani,3 Donatella Sarti3 1ISAL Foundation, Institute for Research on Pain, Torre Pedrera, Rimini, Italy 2Pain Therapy Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 3Department of Pain Therapy and Palliative Care, Infermi Hospital, Rimini, Italy Abstract: Central post-stroke pain (CPSP is still an underestimated complication of stroke, resulting in impaired quality of life and, in addition to the functional and cognitive consequences of stroke, the presence of CPSP may be associated with mood disorders, such as depression, anxiety, and sleep disturbances. This type of pain may also impair activities of daily living and further worsen quality of life, negatively influencing the rehabilitation process. The prevalence of CSPS in the literature is highly variable (1%–12% according to different studies, and this variability could be influenced by selection criteria and the different ethnic populations being investigated. With this scenario in mind, we performed a population-based study to assess the prevalence of CPSP and its main features in a homogeneous health district (Rimini, Italy, including five hospitals for a total population of 329,970 inhabitants. From 2008 to 2010, we selected 1,494 post-stroke patients and were able to interview 660 patients, 66 (11% of whom reported pain with related tactile and thermal hyperesthesia, accompanied by needle puncture, tingling, swelling, and pressure sensations. Patients reported motor impairment and disability, which influenced their working ability, rehabilitation, and social life. Despite this severe pain state, there was a high percentage of patients who did not receive adequate treatment for pain. Keywords: stroke, central post-stroke pain, disability

  5. The major brain endocannabinoid 2-AG controls neuropathic pain and mechanical hyperalgesia in patients with neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Hannah L Pellkofer

    Full Text Available Recurrent myelitis is one of the predominant characteristics in patients with neuromyelitis optica (NMO. While paresis, visual loss, sensory deficits, and bladder dysfunction are well known symptoms in NMO patients, pain has been recognized only recently as another key symptom of the disease. Although spinal cord inflammation is a defining aspect of neuromyelitis, there is an almost complete lack of data on altered somatosensory function, including pain. Therefore, eleven consecutive patients with NMO were investigated regarding the presence and clinical characteristics of pain. All patients were examined clinically as well as by Quantitative Sensory Testing (QST following the protocol of the German Research Network on Neuropathic Pain (DFNS. Additionally, plasma endocannabinoid levels and signs of chronic stress and depression were determined. Almost all patients (10/11 suffered from NMO-associated neuropathic pain for the last three months, and 8 out of 11 patients indicated relevant pain at the time of examination. Symptoms of neuropathic pain were reported in the vast majority of patients with NMO. Psychological testing revealed signs of marked depression. Compared to age and gender-matched healthy controls, QST revealed pronounced mechanical and thermal sensory loss, strongly correlated to ongoing pain suggesting the presence of deafferentation-induced neuropathic pain. Thermal hyperalgesia correlated to MRI-verified signs of spinal cord lesion. Heat hyperalgesia was highly correlated to the time since last relapse of NMO. Patients with NMO exhibited significant mechanical and thermal dysesthesia, namely dynamic mechanical allodynia and paradoxical heat sensation. Moreover, they presented frequently with either abnormal mechanical hypoalgesia or hyperalgesia, which depended significantly on plasma levels of the endogenous cannabinoid 2-arachidonoylglycerole (2-AG. These data emphasize the high prevalence of neuropathic pain and hyperalgesia

  6. Mechanisms-based classifications of musculoskeletal pain: part 2 of 3: symptoms and signs of peripheral neuropathic pain in patients with low back (± leg) pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-08-01

    As a mechanisms-based classification of pain \\'peripheral neuropathic pain\\' (PNP) refers to pain arising from a primary lesion or dysfunction in the peripheral nervous system. Symptoms and signs associated with an assumed dominance of PNP in patients attending for physiotherapy have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of PNP in patients with low back (± leg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (± leg) pain were assessed using a standardised assessment protocol. Patients\\' pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist specifying the presence or absence of various clinical criteria. A binary logistic regression analysis with Bayesian model averaging identified a cluster of two symptoms and one sign predictive of PNP, including: \\'Pain referred in a dermatomal or cutaneous distribution\\

  7. Double-Cone Coil TMS Stimulation of the Medial Cortex Inhibits Central Pain Habituation.

    Directory of Open Access Journals (Sweden)

    Federico D'Agata

    Full Text Available The aim of this study was to investigate whether Transcranial Magnetic Stimulation (TMS applied over the medial line of the scalp affects the subjective perception of continuous pain induced by means of electric stimulation. In addition, we wanted to identify the point of stimulation where this effect was maximum.Superficial electrical stimulation was used to induce continuous pain on the dominant hand. At the beginning of the experiment we reached a pain rating of 5 on an 11-point numeric rating scale (NRS; 0 = no pain and 10 = maximum tolerable pain for each subject by setting individually the current intensity. The TMS (five pulses at increasing intensities was applied on 5 equidistant points (one per session over the medial line of the scalp in 13 healthy volunteers using a double-cone coil to stimulate underlying parts of the brain cortex. In every experimental session the painful stimulation lasted 45 minutes, during which pain and distress intensities NRS were recorded continuously. We calculated the effect of adaptation and the immediate effect of the TMS stimulation for all locations. Additionally, an ALE (Activation Likelihood Estimation meta-analysis was performed to compare our results with the neuroimaging literature on subjective pain rating.TMS stimulation temporarily decreased the pain ratings, and pain adaptation was suppressed when applying the TMS over the FCz site on the scalp. No effect was found for distress ratings.The present data suggest that the medial cortex in proximity of the cingulated gyrus has a causal role in adaptation mechanisms and in processing ongoing pain and subjective sensation of pain intensity.

  8. Pharmacological management of central post-stroke pain: a practical guide.

    Science.gov (United States)

    Kim, Jong S

    2014-09-01

    Pain is one of the most troublesome sequelae of stroke. Some of this post-stroke pain is caused by the brain lesion itself; this is called central post-stroke pain (CPSP). Although the prevalence of CPSP is low (1-8 %), persistent, often treatment-resistant, painful sensations are a major problem for stroke patients. The pathogenesis of CPSP remains unknown, but suggested underlying causes include hyperexcitation in the damaged sensory pathways, damage to the central inhibitory pathways, or a combination of the two. For pharmacological treatment, amitriptyline, an adrenergic antidepressant, is currently the first-line drug for CPSP. However, its effect is frequently incomplete and a high dose is commonly not tolerated in stroke patients. Lamotrigine, an antiepileptic, was also found to be effective in a controlled trial and can be used as an alternative or additive therapy. GABAergic drugs with potential calcium channel-blocking effects, such as gabapentin or pregabalin, have recently emerged as a potentially useful therapy. These drugs are effective in various neuropathic pain syndromes, but their effect on CPSP remains to be proven. Pregabalin may improve pain-related anxiety and sleep disturbances. Fluvoxamine and mexiletine may be used adjunctively in some patients. Non-pharmacological treatments such as motor cortex stimulation or deep brain stimulation are used in some centers, but are not proven to be effective. Further well designed clinical trials as well as basic research should be performed to improve our understanding of the pathophysiology of CPSP and to develop better treatment strategies.

  9. Central effect of histamine in a rat model of acute trigeminal pain.

    Science.gov (United States)

    Tamaddonfard, Esmaeal; Khalilzadeh, Emad; Hamzeh-Gooshchi, Nasrin; Seiednejhad-Yamchi, Sona

    2008-01-01

    In conscious rats implanted with an intracerebroventricular (icv) cannula, effect of icv injections of histamine, chlorpheniramine (H(1)-receptor antagonist) and ranitidine (H(2)-receptor blocker) was investigated in a rat model of acute trigeminal pain. Acute trigeminal pain was induced by putting a drop of 5 M NaCl solution on the corneal surface of the eye and the numbers of eye wipes were counted during the first 30 s. Histamine (20, 40 microg) and chlorpheniramine (80 microg) significantly decreased the numbers of eye wipes. Ranitidine alone had no effect. Pretreatment with chlorpheniramine did not change the histamine-induced analgesia, whereas the histamine effect on pain was inhibited with ranitidine pretreatment. These results indicate that the brain histamine, through central H(2) receptors, may be involved in the modulation of the acute trigeminal pain in rats.

  10. Does Acupuncture Alter Pain-related Functional Connectivity of the Central Nervous System? A Systematic Review.

    Science.gov (United States)

    Villarreal Santiago, María; Tumilty, Steve; Mącznik, Aleksandra; Mani, Ramakrishnan

    2016-08-01

    Acupuncture has been studied for several decades to establish evidence-based clinical practice. This systematic review aims to evaluate evidence for the effectiveness of acupuncture in influencing the functional connectivity of the central nervous system in patients with musculoskeletal pain. A systematic search of the literature was conducted to identify studies in which the central response of acupuncture in patients with musculoskeletal pain was evaluated by neuroimaging techniques. Databases searched were AMED, CINAHL, Cochrane Library, EMBASE, MEDLINE, PEDro, Pubmed, SCOPUS, SPORTDiscuss, and Web of Science. Included studies were assessed by two independent reviewers for their methodological quality by using the Downs and Black questionnaire and for their levels of completeness and transparency in reporting acupuncture interventions by using Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) criteria. Seven studies met the inclusion criteria. Three studies were randomized controlled trials (RCTs) and four studies were nonrandomized controlled trials (NRCTs). The neuroimaging techniques used were functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Positive effects on the functional connectivity of the central nervous system more consistently occurred during long-term acupuncture treatment. The results were heterogeneous from a descriptive perspective; however, the key findings support acupuncture's ability to alter pain-related functional connectivity in the central nervous system in patients with musculoskeletal pain.

  11. Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

    Science.gov (United States)

    Saloman, Jami L.

    Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand

  12. Does pre-surgical central modulation of pain influence outcome after total knee replacement? A systematic review.

    Science.gov (United States)

    Baert, I A C; Lluch, E; Mulder, T; Nijs, J; Noten, S; Meeus, M

    2016-02-01

    The aim of this study is to systematically review whether the presence of altered central pain modulation pre-surgical influences outcome after total knee replacement (TKR) in patients with knee osteoarthritis (OA), and if so which indices of central pain modulation predict poor outcome after TKR. To identify relevant articles, PubMed and Web of Science were searched. The search strategy was a combination of key words related to "Knee Osteoarthritis and Total Knee Replacement", "Central Pain Modulation" and "Post-Surgical Outcome Measures". Articles fulfilling the inclusion criteria were screened for methodological quality and results were analyzed and summarized. Sixteen prospective cohort studies were included. Strong evidence is available that presence of catastrophic thinking and poor coping strategies predict more pain after TKR and that there is no association between fear of movement and post-surgical pain or function. Evidence on other psychosocial influences is limited or conflicting. Literature on the influence of other signs of altered central pain modulation on post-surgical outcome is scarce. It is plausible that pre-surgical signs of altered central pain modulation, such as joint pain at rest or widespread pain sensitization, predict more post-surgical pain. Surgeons should be attentive for patients with signs of altered central pain modulation before surgery as they might be at risk for unfavorable outcome. A broader therapeutic approach aiming to desensitize the central nervous system can be adapted in these patients. Further research is however needed to identify the influence of central pain modulation pre-surgical in predicting outcome after TKR.

  13. Central pain processing in chronic chemotherapy-induced peripheral neuropathy: a functional magnetic resonance imaging study.

    Directory of Open Access Journals (Sweden)

    Elaine G Boland

    Full Text Available Life expectancy in multiple myeloma has significantly increased. However, a high incidence of chemotherapy induced peripheral neuropathy (CIPN can negatively influence quality of life during this period. This study applied functional magnetic resonance imaging (fMRI to compare areas associated with central pain processing in patients with multiple myeloma who had chemotherapy induced peripheral neuropathy (MM-CIPN with those from healthy volunteers (HV. Twenty-four participants (n = 12 MM-CIPN, n = 12 HV underwent Blood Oxygen Level-Dependent (BOLD fMRI at 3T whilst noxious heat-pain stimuli were applied to the foot and then thigh. Patients with MM-CIPN demonstrated greater activation during painful stimulation in the precuneus compared to HV (p = 0.014, FWE-corrected. Patients with MM-CIPN exhibited hypo-activation of the right superior frontal gyrus compared to HV (p = 0.031, FWE-corrected. Significant positive correlation existed between the total neuropathy score (reduced version and activation in the frontal operculum (close to insular cortex during foot stimulation in patients with MM-CIPN (p = 0.03, FWE-corrected; adjusted R2 = 0.87. Painful stimuli delivered to MM-CIPN patients evoke differential activation of distinct cortical regions, reflecting a unique pattern of central pain processing compared with healthy volunteers. This characteristic activation pattern associated with pain furthers the understanding of the pathophysiology of painful chemotherapy induced peripheral neuropathy. Functional MRI provides a tool for monitoring cerebral changes during anti-cancer and analgesic treatment.

  14. Reduction of central neuropathic pain with ketamine infusion in a patient with Ehlers–Danlos syndrome: a case report

    Science.gov (United States)

    Lo, Tony Chung Tung; Yeung, Stephen Tung; Lee, Sujin; Skavinski, Kira; Liao, Solomon

    2016-01-01

    Objective Ehlers–Danlos syndrome frequently causes acute and chronic pain because of joint subluxations and dislocations secondary to hypermobility. Current treatments for pain related to Ehlers–Danlos syndrome and central pain syndrome are inadequate. This case report discusses the therapeutic use of ketamine intravenous infusion as an alternative. Case report A 27-year-old Caucasian female with a history of Ehlers–Danlos syndrome and spinal cord ischemic myelopathy resulting in central pain syndrome, presented with severe generalized body pain refractory to multiple pharmacological interventions. After a 7-day course of ketamine intravenous infusion under controlled generalized sedation in the intensive care unit, the patient reported a dramatic reduction in pain levels from 7–8 out of 10 to 0–3 out of 10 on a numeric rating scale and had a significant functional improvement. The patient tolerated a reduction in her pain medication regimen, which originally included opioids, gabapentin, pregabalin, tricyclic antidepressants, and nonsteroidal anti-inflammatory drugs. Conclusion Ketamine infusion treatment has been used in various pain syndromes, including central neuropathic pain, ischemic pain, and regional pain syndrome. Reports have suggested that ketamine modulates pain by the regression of N-methyl-D-aspartate receptor to a resting state. As such, propagation of nociceptive signal to brain is interrupted allowing for the restoration of physiological balance between pain inhibition and facilitation. The present report shows that this treatment option can be used in patients with refractory central pain syndrome in the setting of spinal cord myelopathy secondary to Ehlers–Danlos syndrome. In addition, as seen in this case, this protocol can potentially decrease the chronic use of pain medication, such as opioids.

  15. Safety and efficacy of pregabalin in patients with central post-stroke pain.

    Science.gov (United States)

    Kim, Jong S; Bashford, Guy; Murphy, T Kevin; Martin, Andrew; Dror, Vardit; Cheung, Raymond

    2011-05-01

    Pregabalin has demonstrated efficacy in several forms of neuropathic pain, but its long-term efficacy in central post-stroke pain (CPSP) is unproven. We evaluated the efficacy and safety of pregabalin versus placebo in patients with CPSP. A 13-week, randomized, double-blind, multicenter, placebo-controlled, parallel group study of 150 to 600 mg/day pregabalin was conducted in patients aged ≥18 years with CPSP. The primary efficacy endpoint was the mean pain score on the Daily Pain Rating Scale over the last 7 days on study drug up to week 12 or early termination visit. Secondary endpoints included other pain parameters and patient-reported sleep and health-related quality-of-life measures. A total of 219 patients were treated (pregabalin n=110; placebo n=109). A mean pain score at baseline of 6.5 in the pregabalin group and 6.3 in the placebo group reduced at endpoint to 4.9 in the pregabalin group and 5.0 in the placebo group (LS mean difference=-0.2; 95% CI=-0.7, 0.4; P=0.578). Treatment with pregabalin resulted in significant improvements, compared with placebo, on secondary endpoints including MOS-sleep, HADS-A anxiety, and clinician global impression of change (CGIC) Ppain reductions at endpoint did not differ significantly between pregabalin and placebo, improvements in sleep, anxiety, and CGIC suggest some utility of pregabalin in the management of CPSP.

  16. Targeting P(2)X(7) receptor for the treatment of central post-stroke pain in a rodent model.

    Science.gov (United States)

    Kuan, Yung-Hui; Shih, Hsi-Chien; Tang, Sung-Chun; Jeng, Jiann-Shing; Shyu, Bai-Chuang

    2015-06-01

    Stroke is a leading cause of death and disability in industrialized countries. Approximately 8-14% of stroke survivors suffer from central post-stroke pain (CPSP) when hemorrhagic stroke occurs in lateral thalamic regions, which severely affects their quality of life. Because the mechanisms of CPSP are not well understood, effective treatments have not been developed. In the present study, we tested the hypothesis that persistent CPSP is caused by P(2)X(7)receptor activation after brain tissue damage and subsequent elevations in inflammatory cytokines. A thalamic hemorrhagic rat model was used, characterized by thermal and mechanical allodynia that develops in the subacute to chronic phases upon CPSP onset. We found a significant increase in P(2)X(7) expression in reactive microglia/macrophages in thalamic peri-lesion tissues at 5 weeks post-hemorrhage. Thalamic P(2)X(7) receptors were directly involved in pain transmission and hypersensitivity. The systemic targeting of P(2)X(7) receptors during the acute stage of hemorrhage rescued abnormal pain behaviors and neuronal activity in the thalamocingulate pathway by reducing reactive microglia/macrophage aggregation and associated inflammatory cytokines. After CPSP onset, the targeting of interleukin-1β reversed abnormal pain sensitivity. The aberrant spontaneous thalamocortical oscillations in rats with CPSP were modulated by blocking P(2)X(7) receptors. Taken together, our results suggest that targeting P(2)X(7) may be bi-effective in the treatment of CPSP, as both a pain blocker and immunosuppressant that inhibits inflammatory damage to brain tissue. P(2)X(7)receptors may serve as a potential target to prevent the occurrence of CPSP and may be beneficial for the recovery of patients from stroke.

  17. Atypical central pain processing in sensory modulation disorder: absence of temporal summation and higher after-sensation.

    Science.gov (United States)

    Bar-Shalita, T; Vatine, J-J; Yarnitsky, D; Parush, S; Weissman-Fogel, I

    2014-02-01

    Sensory over-responsivity (SOR), a subtype of the proposed sensory modulation disorder (SMD), is characterized by over-responsiveness to stimuli in several sensory modalities. SMD individuals demonstrate abnormal responses to naturally occurring stimuli in a manner that interferes with daily life participation. Previous psychophysical testing of the somatosensory system revealed that SOR individuals rated pain sensations higher than controls, demonstrating hyperalgesia that can be centrally mediated. Temporal summation (TS) of second pain and after-sensation are manifestations of central sensitization; therefore, this study explored these measures for better characterization of central pain processing in SOR. Twelve SOR adults and 12 healthy controls participated. TS was produced by a train of fifteen repetitive heat pulses, 0.7 s duration each, and 2 s of inter-stimulus interval, applied to the thenar-eminence, while four pain ratings were obtained. An after-sensation was then measured for 5 min, obtaining six pain ratings. No TS of pain was indicated in the SOR group (SOR: p = 0.36; control: p pain after-sensation, individuals with SOR continued to report pain for the duration of the 5 min measured (p = 0.002). These results demonstrate an atypical response pattern, suggesting alteration in pain processing and/or modulation at a central level in individuals with SOR. These possible neural changes may manifest themselves as interference with daily functioning as well as shed light on some of the between-subject variability seen in psychophysical testing in non-painful subjects.

  18. Recombinant neural progenitor transplants in the spinal dorsal horn alleviate chronic central neuropathic pain.

    Science.gov (United States)

    Jergova, Stanislava; Gajavelli, Shyam; Pathak, Nirmal; Sagen, Jacqueline

    2016-04-01

    Neuropathic pain induced by spinal cord injury (SCI) is clinically challenging with inadequate long-term treatment options. Partial pain relief offered by pharmacologic treatment is often counterbalanced by adverse effects after prolonged use in chronic pain patients. Cell-based therapy for neuropathic pain using GABAergic neuronal progenitor cells (NPCs) has the potential to overcome untoward effects of systemic pharmacotherapy while enhancing analgesic potency due to local activation of GABAergic signaling in the spinal cord. However, multifactorial anomalies underlying chronic pain will likely require simultaneous targeting of multiple mechanisms. Here, we explore the analgesic potential of genetically modified rat embryonic GABAergic NPCs releasing a peptidergic NMDA receptor antagonist, Serine-histogranin (SHG), thus targeting both spinal hyperexcitability and reduced inhibitory processes. Recombinant NPCs were designed using either lentiviral or adeno-associated viral vectors (AAV2/8) encoding single and multimeric (6 copies of SHG) cDNA. Intraspinal injection of recombinant cells elicited enhanced analgesic effects compared with nonrecombinant NPCs in SCI-induced pain in rats. Moreover, potent and sustained antinociception was achieved, even after a 5-week postinjury delay, using recombinant multimeric NPCs. Intrathecal injection of SHG antibody attenuated analgesic effects of the recombinant grafts suggesting active participation of SHG in these antinociceptive effects. Immunoblots and immunocytochemical assays indicated ongoing recombinant peptide production and secretion in the grafted host spinal cords. These results support the potential for engineered NPCs grafted into the spinal dorsal horn to alleviate chronic neuropathic pain.

  19. Potential mechanisms supporting the value of motor cortex stimulation to treat chronic pain syndromes

    Directory of Open Access Journals (Sweden)

    Marcos Fabio DosSantos

    2016-02-01

    Full Text Available Throughout the first years of the twenty-first century, neurotechnologies such as motor cortex stimulation (MCS, transcranial magnetic stimulation (TMS and transcranial direct current stimulation (tDCS have attracted scientific attention and been considered as potential tools to centrally modulate chronic pain, especially for those conditions more difficult to manage and refractory to all types of available pharmacological therapies. Interestingly, although the role of the motor cortex in pain has not been fully clarified, it is one of the cortical areas most commonly targeted by invasive and non-invasive neuromodulation technologies. Recent studies have provided significant advances concerning the establishment of the clinical effectiveness of primary motor cortex stimulation to treat different chronic pain syndromes. Concurrently, the neuromechanisms related to each method of primary motor cortex (M1 modulation have been unveiled. In this respect, the most consistent scientific evidence originates from MCS studies, which indicate the activation of top-down controls driven by M1 stimulation. This concept has also been applied to explain M1-TMS mechanisms. Nevertheless, activation of remote areas in the brain, including cortical and subcortical structures, has been reported with both invasive and non-invasive methods and the participation of major neurotransmitters (e.g. glutamate, GABA and serotonin as well as the release of endogenous opioids has been demonstrated. In this critical review, the putative mechanisms underlying the use of motor cortex stimulation to provide relief from chronic migraine and other types of chronic pain are discussed. Emphasis is placed on the most recent scientific evidence obtained from chronic pain research studies involving MCS and non-invasive neuromodulation methods (e.g. tDCS and TMS, which are analyzed comparatively.

  20. Potential Mechanisms Supporting the Value of Motor Cortex Stimulation to Treat Chronic Pain Syndromes

    Science.gov (United States)

    DosSantos, Marcos F.; Ferreira, Natália; Toback, Rebecca L.; Carvalho, Antônio C.; DaSilva, Alexandre F.

    2016-01-01

    Throughout the first years of the twenty-first century, neurotechnologies such as motor cortex stimulation (MCS), transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS) have attracted scientific attention and been considered as potential tools to centrally modulate chronic pain, especially for those conditions more difficult to manage and refractory to all types of available pharmacological therapies. Interestingly, although the role of the motor cortex in pain has not been fully clarified, it is one of the cortical areas most commonly targeted by invasive and non-invasive neuromodulation technologies. Recent studies have provided significant advances concerning the establishment of the clinical effectiveness of primary MCS to treat different chronic pain syndromes. Concurrently, the neuromechanisms related to each method of primary motor cortex (M1) modulation have been unveiled. In this respect, the most consistent scientific evidence originates from MCS studies, which indicate the activation of top-down controls driven by M1 stimulation. This concept has also been applied to explain M1-TMS mechanisms. Nevertheless, activation of remote areas in the brain, including cortical and subcortical structures, has been reported with both invasive and non-invasive methods and the participation of major neurotransmitters (e.g., glutamate, GABA, and serotonin) as well as the release of endogenous opioids has been demonstrated. In this critical review, the putative mechanisms underlying the use of MCS to provide relief from chronic migraine and other types of chronic pain are discussed. Emphasis is placed on the most recent scientific evidence obtained from chronic pain research studies involving MCS and non-invasive neuromodulation methods (e.g., tDCS and TMS), which are analyzed comparatively. PMID:26903788

  1. Analysis of deep tissue hypersensitivity to pressure pain in professional pianists with insidious mechanical neck pain

    OpenAIRE

    2011-01-01

    Abstract Background The aim of this study was to investigate whether pressure pain hyperalgesia is a feature of professional pianists suffering from neck pain as their main playing-related musculoskeletal disorder. Methods Twenty-three active expert pianists, 6 males and 17 females (age: 36 ± 12 years) with insidious neck pain and 23 pianists, 9 males and 14 females (age: 38 ± 10 years) without neck pain the previous year were recruited. A numerical pain rate scale, Neck Disability Index, han...

  2. Diagnosis and classification of chronic low back pain disorders: maladaptive movement and motor control impairments as underlying mechanism.

    Science.gov (United States)

    O'Sullivan, Peter

    2005-11-01

    Low back pain (LBP) is a very common but largely self-limiting condition. The problem arises however, when LBP disorders do not resolve beyond normal expected tissue healing time and become chronic. Eighty five percent of chronic low back pain (CLBP) disorders have no known diagnosis leading to a classification of 'non-specific CLBP' that leaves a diagnostic and management vacuum. Even when a specific radiological diagnosis is reached the underlying pain mechanism cannot always be assumed. It is now widely accepted that CLBP disorders are multi-factorial in nature. However the presence and dominance of the patho-anatomical, physical, neuro-physiological, psychological and social factors that can influence the disorder is different for each individual. Classification of CLBP pain disorders into sub-groups, based on the mechanism underlying the disorder, is considered critical to ensure appropriate management. It is proposed that three broad sub-groups of CLBP disorders exist. The first group of disorders present where underlying pathological processes drive the pain, and the patients' motor responses in the disorder are adaptive. A second group of disorders present where psychological and/or social factors represent the primary mechanism underlying the disorder that centrally drives pain, and where the patient's coping and motor control strategies are mal-adaptive in nature. Finally it is proposed that there is a large group of CLBP disorders where patients present with either movement impairments (characterized by pain avoidance behaviour) or control impairments (characterized by pain provocation behaviour). These pain disorders are predominantly mechanically induced and patients typically present with mal-adaptive primary physical and secondary cognitive compensations for their disorders that become a mechanism for ongoing pain. These subjects present either with an excess or deficit in spinal stability, which underlies their pain disorder. For this group

  3. New Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain

    DEFF Research Database (Denmark)

    Feldman, Eva L; Nave, Klaus-Armin; Jensen, Troels Staehelin

    2017-01-01

    the mechanisms underlying diabetic neuropathy (DN). In this review, we present the structural components of the peripheral nervous system that underlie its susceptibility to metabolic insults and then discuss the pathways that contribute to peripheral nerve injury in DN. We also discuss systems biology insights......Pre-diabetes and diabetes are a global epidemic, and the associated neuropathic complications create a substantial burden on both the afflicted patients and society as a whole. Given the enormity of the problem and the lack of effective therapies, there is a pressing need to understand...... gleaned from the recent advances in biotechnology and bioinformatics, emerging ideas centered on the axon-Schwann cell relationship and associated bioenergetic crosstalk, and the rapid expansion of our knowledge of the mechanisms contributing to neuropathic pain in diabetes. These recent advances in our...

  4. MrgC agonism at central terminals of primary sensory neurons inhibits neuropathic pain.

    Science.gov (United States)

    He, Shao-Qiu; Li, Zhe; Chu, Yu-Xia; Han, Liang; Xu, Qian; Li, Man; Yang, Fei; Liu, Qin; Tang, Zongxiang; Wang, Yun; Hin, Niyada; Tsukamoto, Takashi; Slusher, Barbara; Tiwari, Vinod; Shechter, Ronen; Wei, Feng; Raja, Srinivasa N; Dong, Xinzhong; Guan, Yun

    2014-03-01

    Chronic neuropathic pain is often refractory to current pharmacotherapies. The rodent Mas-related G-protein-coupled receptor subtype C (MrgC) shares substantial homogeneity with its human homologue, MrgX1, and is located specifically in small-diameter dorsal root ganglion neurons. However, evidence regarding the role of MrgC in chronic pain conditions has been disparate and inconsistent. Accordingly, the therapeutic value of MrgX1 as a target for pain treatment in humans remains uncertain. Here, we found that intrathecal injection of BAM8-22 (a 15-amino acid peptide MrgC agonist) and JHU58 (a novel dipeptide MrgC agonist) inhibited both mechanical and heat hypersensitivity in rats after an L5 spinal nerve ligation (SNL). Intrathecal JHU58-induced pain inhibition was dose dependent in SNL rats. Importantly, drug efficacy was lost in Mrg-cluster gene knockout (Mrg KO) mice and was blocked by gene silencing with intrathecal MrgC siRNA and by a selective MrgC receptor antagonist in SNL rats, suggesting that the drug action is MrgC dependent. Further, in a mouse model of trigeminal neuropathic pain, microinjection of JHU58 into ipsilateral subnucleus caudalis inhibited mechanical hypersensitivity in wild-type but not Mrg KO mice. Finally, JHU58 attenuated the miniature excitatory postsynaptic currents frequency both in medullary dorsal horn neurons of mice after trigeminal nerve injury and in lumbar spinal dorsal horn neurons of mice after SNL. We provide multiple lines of evidence that MrgC agonism at spinal but not peripheral sites may constitute a novel pain inhibitory mechanism that involves inhibition of peripheral excitatory inputs onto postsynaptic dorsal horn neurons in different rodent models of neuropathic pain.

  5. Effects of dexmedetomidine on procedural pain and discomfort associated with central venous catheter insertion

    Directory of Open Access Journals (Sweden)

    Aloka Samantaray

    2014-01-01

    Full Text Available Background and Aim: Central venous catheter (CVC insertion induces pain and discomfort to a conscious patient despite application of a local anaesthetic (LA field block and this pain can be greatly lessened by using additional analgesics. The aim of this study was to evaluate the efficacy of dexmedetomidine along with LA field infiltration in controlling pain and discomfort associated with CVC insertion. Methods: A prospective, randomised, double-blind, placebo-controlled trial of 54 patients scheduled for planned CVC insertion was undertaken. Patients were randomly assigned into two groups of 27 each, to receive either dexmedetomidine (1 μg/kg or 0.9% normal saline, along with LA field infiltration. Pain and discomfort score was measured at 5 time points. Results: The median pain score was worst for placebo group at local anaesthetic injection (6 [4-7] and at the end of procedure (5 [4-5], which was significantly attenuated in the dexmedetomidine group (4 [4-5] and 4 [3-5]; P = 0.007 and 0.040 respectively. The lower procedure related discomfort score in the immediate post-procedural period was statistically significant in dexmedetomidine group compared to placebo (4 [4-5] vs. 5 [4-6]; P = 0.008. Conclusions: Pre-procedural bolus dexmedetomidine infusion provides adequate analgesia and patient comfort for CVC insertion along LA field block. However, the tendency for excessive sedation and bradycardia associated with dexmedetomidine render it less desirable for this purpose.

  6. The Cortical Signature of Central Poststroke Pain: Gray Matter Decreases in Somatosensory, Insular, and Prefrontal Cortices.

    Science.gov (United States)

    Krause, T; Asseyer, S; Taskin, B; Flöel, A; Witte, A V; Mueller, K; Fiebach, J B; Villringer, K; Villringer, A; Jungehulsing, G J

    2016-01-01

    It has been proposed that cortical structural plasticity plays a crucial role in the emergence and maintenance of chronic pain. Various distinct pain syndromes have accordingly been linked to specific patterns of decreases in regional gray matter volume (GMV). However, it is not known whether central poststroke pain (CPSP) is also associated with cortical structural plasticity. To determine this, we employed T1-weighted magnetic resonance imaging at 3 T and voxel-based morphometry in 45 patients suffering from chronic subcortical sensory stroke with (n = 23) and without CPSP (n = 22), and healthy matched controls (n = 31). CPSP patients showed decreases in GMV in comparison to healthy controls, involving secondary somatosensory cortex (S2), anterior as well as posterior insular cortex, ventrolateral prefrontal and orbitofrontal cortex, temporal cortex, and nucleus accumbens. Comparing CPSP patients to nonpain patients revealed a similar but more restricted pattern of atrophy comprising S2, ventrolateral prefrontal and temporal cortex. Additionally, GMV in the ventromedial prefrontal cortex negatively correlated to pain intensity ratings. This shows for the first time that CPSP is accompanied by a unique pattern of widespread structural plasticity, which involves the sensory-discriminative areas of insular/somatosensory cortex, but also expands into prefrontal cortex and ventral striatum, where emotional aspects of pain are processed.

  7. Reduction of central neuropathic pain with ketamine infusion in a patient with Ehlers–Danlos syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Lo TC

    2016-09-01

    Full Text Available Tony Chung Tung Lo,1,* Stephen Tung Yeung,2,* Sujin Lee,1 Kira Skavinski,3 Solomon Liao,4 1Department of Physical Medicine and Rehabilitation, University of California Irvine, Orange, CA, 2Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, 3Department of Palliative Medicine, University of California San Diego, La Jolla, 4Department of Palliative Medicine, University of California Irvine, Orange, CA, USA *These authors contributed equally to this work Objective: Ehlers–Danlos syndrome frequently causes acute and chronic pain because of joint subluxations and dislocations secondary to hypermobility. Current treatments for pain related to Ehlers–Danlos syndrome and central pain syndrome are inadequate. This case report discusses the therapeutic use of ketamine intravenous infusion as an alternative. Case report: A 27-year-old Caucasian female with a history of Ehlers–Danlos syndrome and spinal cord ischemic myelopathy resulting in central pain syndrome, presented with severe generalized body pain refractory to multiple pharmacological interventions. After a 7-day course of ketamine intravenous infusion under controlled generalized sedation in the intensive care unit, the patient reported a dramatic reduction in pain levels from 7–8 out of 10 to 0–3 out of 10 on a numeric rating scale and had a significant functional improvement. The patient tolerated a reduction in her pain medication regimen, which originally included opioids, gabapentin, pregabalin, tricyclic antidepressants, and nonsteroidal anti-inflammatory drugs. Conclusion: Ketamine infusion treatment has been used in various pain syndromes, including central neuropathic pain, ischemic pain, and regional pain syndrome. Reports have suggested that ketamine modulates pain by the regression of N-methyl-D-aspartate receptor to a resting state. As such, propagation of nociceptive signal to brain is interrupted allowing for the restoration of

  8. Back pain in space and post-flight spine injury: Mechanisms and countermeasure development

    Science.gov (United States)

    Sayson, Jojo V.; Lotz, Jeffrey; Parazynski, Scott; Hargens, Alan R.

    2013-05-01

    During spaceflight many astronauts experience moderate to severe lumbar pain and deconditioning of paraspinal muscles. There is also a significant incidence of herniated nucleus pulposus (HNP) in astronauts post-flight being most prevalent in cervical discs. Relief of in-flight lumbar back pain is facilitated by assuming a knee-to-chest position. The pathogenesis of lumbar back pain during spaceflight is most likely discogenic and somatic referred (from the sinuvertebral nerves) due to supra-physiologic swelling of the lumbar intervertebral discs (IVDs) due to removal of gravitational compressive loads in microgravity. The knee-to-chest position may reduce lumbar back pain by redistributing stresses through compressive loading to the IVDs, possibly reducing disc volume by fluid outflow across IVD endplates. IVD stress redistribution may reduce Type IV mechanoreceptor nerve impulse propagation in the annulus fibrosus and vertebral endplate resulting in centrally mediated pain inhibition during spinal flexion. Countermeasures for lumbar back pain may include in-flight use of: (1) an axial compression harness to prevent excessive IVD expansion and spinal column elongation; (2) the use of an adjustable pulley exercise developed to prevent atrophy of spine muscle stabilisers; and (3) other exercises that provide Earth-like annular stress with low-load repetitive active spine rotation movements. The overall objective of these countermeasures is to promote IVD health and to prevent degenerative changes that may lead to HNPs post-flight. In response to "NASA's Critical Path Roadmap Risks and Questions" regarding disc injury and higher incidence of HNPs after space flight (Integrated Research Plan Gap-B4), future studies will incorporate pre- and post-flight imaging of International Space Station long-duration crew members to investigate mechanisms of lumbar back pain as well as degeneration and damage to spinal structures. Quantitative results on morphological, biochemical

  9. Analysis of deep tissue hypersensitivity to pressure pain in professional pianists with insidious mechanical neck pain

    Directory of Open Access Journals (Sweden)

    Linari-Melfi Marcela

    2011-11-01

    Full Text Available Abstract Background The aim of this study was to investigate whether pressure pain hyperalgesia is a feature of professional pianists suffering from neck pain as their main playing-related musculoskeletal disorder. Methods Twenty-three active expert pianists, 6 males and 17 females (age: 36 ± 12 years with insidious neck pain and 23 pianists, 9 males and 14 females (age: 38 ± 10 years without neck pain the previous year were recruited. A numerical pain rate scale, Neck Disability Index, hand size and pressure pain thresholds (PPT were assessed bilaterally over the C5-C6 zygapophyseal joint, deltoid muscle, the second metacarpal and the tibialis anterior muscle in a blinded design. Results The results showed that PPT levels were significantly decreased bilaterally over the second metacarpal and tibialis anterior muscles (P 0.10, in pianists with neck pain as compared to healthy pianists. Pianists with neck pain had a smaller (P Conclusions Our findings revealed pressure pain hypersensitivity over distant non-symptomatic distant points but not over the symptomatic areas in pianists suffering from neck pain. In addition, pianists with neck pain also had smaller hand size than those without neck pain. Future studies are needed to further determine the relevance of these findings in the clinical course of neck pain as playing-related musculoskeletal disorder in professional pianists.

  10. Pain genes.

    Directory of Open Access Journals (Sweden)

    Tom Foulkes

    2008-07-01

    Full Text Available Pain, which afflicts up to 20% of the population at any time, provides both a massive therapeutic challenge and a route to understanding mechanisms in the nervous system. Specialised sensory neurons (nociceptors signal the existence of tissue damage to the central nervous system (CNS, where pain is represented in a complex matrix involving many CNS structures. Genetic approaches to investigating pain pathways using model organisms have identified the molecular nature of the transducers, regulatory mechanisms involved in changing neuronal activity, as well as the critical role of immune system cells in driving pain pathways. In man, mapping of human pain mutants as well as twin studies and association studies of altered pain behaviour have identified important regulators of the pain system. In turn, new drug targets for chronic pain treatment have been validated in transgenic mouse studies. Thus, genetic studies of pain pathways have complemented the traditional neuroscience approaches of electrophysiology and pharmacology to give us fresh insights into the molecular basis of pain perception.

  11. Spinal pain

    Energy Technology Data Exchange (ETDEWEB)

    Izzo, R., E-mail: roberto1766@interfree.it [Neuroradiology Department, A. Cardarelli Hospital, Naples (Italy); Popolizio, T., E-mail: t.popolizio1@gmail.com [Radiology Department, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (Fg) (Italy); D’Aprile, P., E-mail: paoladaprile@yahoo.it [Neuroradiology Department, San Paolo Hospital, Bari (Italy); Muto, M., E-mail: mutomar@tiscali.it [Neuroradiology Department, A. Cardarelli Hospital, Napoli (Italy)

    2015-05-15

    Highlights: • Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional spinal pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally invasive interventional techniques. • Special attention will be given to the discogenic pain, actually considered as the most frequent cause of chronic low back pain. • The correct distinction between referred pain and radicular pain contributes to give a more correct approach to spinal pain. • The pathogenesis of chronic pain renders this pain a true pathology requiring a specific management. - Abstract: The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide [1]. LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic

  12. Painful Diabetic Peripheral Neuropathy: Presentations, Mechanisms, and Exercise Therapy.

    Science.gov (United States)

    Yoo, Min; Sharma, Neena; Pasnoor, Mamatha; Kluding, Patricia M

    2013-06-30

    Diabetic peripheral neuropathy (DPN) is a frequent complication of diabetes and a major cause of morbidity and increased mortality. It is typically characterized by significant deficits in tactile sensitivity, vibration sense, lower-limb proprioception, and kinesthesia. Painful diabetic neuropathy (P-DPN) is a common phenotype of DPN that affects up to one-third of the general diabetic population. P-DPN has been shown to be associated with significant reductions in overall quality of life, increased levels of anxiety and depression, sleep impairment, and greater gait variability. The purpose of this review is to examine proposed mechanisms of P-DPN, summarize current treatment regimen, and assess exercise as a potential therapy for P-PDN. Although exercise has been shown to be an effective therapeutic modality for diabetes, its specific effects on DPN and especially the painful phenotype have not been sufficiently investigated in current literature. Several rodent models and clinical trials have presented promising results in this area, and warrant further investigations examining the effect of exercise on P-DPN.

  13. Analgesia in conjunction with normalisation of thermal sensation following deep brain stimulation for central post-stroke pain.

    Science.gov (United States)

    Pickering, Anthony E; Thornton, Simon R; Love-Jones, Sarah J; Steeds, Charlotte; Patel, Nikunj K

    2009-12-15

    The aetiology of central post-stroke pain (CPSP) is poorly understood and such pains are often refractory to treatment. We report the case of a 56-year-old man, who, following a temporo-parietal infarct, suffered from debilitating and refractory hemi-body cold dysaesthesia and severe tactile allodynia. This was associated with thermal and tactile hypoaesthesia and hypoalgesia on his affected side. Implantation of a deep brain stimulating electrode in his periventricular gray (PVG) region produced an improvement in his pain that was associated with a striking normalisation of his deficits in somatosensory perception. This improvement in pain and thermal sensibility was reversed as stimulation became less effective, because of increased electrode impedance. Therefore, we postulate that the analgesic benefit may have occurred as a consequence of the normalisation of somatosensory function and we discuss these findings in relation to the theories of central pain generation and the potential to engage useful plasticity in central circuits.

  14. Advances in understanding the mechanisms and management of persistent pain in older adults.

    Science.gov (United States)

    Karp, J F; Shega, J W; Morone, N E; Weiner, D K

    2008-07-01

    Older adults with persistent pain are not simply a chronologically older version of younger pain patients. Pain-related disability in older adults may be driven by pain 'homeostenosis', that is, diminished ability to effectively respond to the stress of persistent pain. Some of the comorbidities of ageing that can contribute to pain homeostenosis include cognitive and physical impairments, increased sensitivity to suprathreshold pain stimuli, medical and psychological comorbidities, altered pharmacokinetics and pharmacodynamics, and social isolation. A key distinction between older and younger individuals with persistent pain is the normal and pathological ageing-associated brain changes. These may alter the expression and experience of pain with impaired descending inhibition and dysfunction of pain gating mechanisms. Cognizance of these brain changes is needed to guide appropriate evaluation and treatment approaches. This paper reviews data that support these ageing-associated phenomena. Specifically, we discuss age-related changes in the brain (both normal and pathological) and in pain physiology; changes in experience and expression of pain that occur with dementia and contribute to pain homeostenosis; and unique aspects of age and pain-associated psychological function and their contribution to disability. We also present data demonstrating changes in brain morphology and neuropsychological performance that accompany persistent non-malignant pain in older adults and the treatment implications of these brain changes. Finally, preliminary data are presented on the efficacy of mindfulness meditation, a treatment that has been examined explicitly in older adults and targets optimizing brain function and descending inhibition.

  15. Cannabinoid CB2 receptors regulate central sensitization and pain responses associated with osteoarthritis of the knee joint.

    Directory of Open Access Journals (Sweden)

    James J Burston

    Full Text Available Osteoarthritis (OA of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies. Inhibitory cannabinoid 2 (CB2 receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that spinal administration of JWH133 inhibited noxious-evoked responses of spinal neurones in the model of OA pain, but not in control rats, indicating a novel spinal role of this target. We further demonstrate dynamic changes in spinal CB2 receptor mRNA and protein expression in an OA pain model. The expression of CB2 receptor protein by both neurones and microglia in the spinal cord was significantly increased in the model of OA. Hallmarks of central sensitization, significant spinal astrogliosis and increases in activity of metalloproteases MMP-2 and MMP-9 in the spinal cord were evident in the model of OA pain. Systemic administration of JWH133 attenuated these markers of central sensitization, providing a neurobiological basis for analgesic effects of the CB2 receptor in this model of OA pain. Analysis of human spinal cord revealed a negative correlation between spinal cord CB2 receptor mRNA and macroscopic knee chondropathy. These data provide new clinically relevant evidence that joint damage and spinal CB2 receptor expression are correlated combined with converging pre-clinical evidence that activation of CB2 receptors inhibits central sensitization and its contribution to the manifestation

  16. Cannabinoid CB2 receptors regulate central sensitization and pain responses associated with osteoarthritis of the knee joint.

    Science.gov (United States)

    Burston, James J; Sagar, Devi Rani; Shao, Pin; Bai, Mingfeng; King, Emma; Brailsford, Louis; Turner, Jenna M; Hathway, Gareth J; Bennett, Andrew J; Walsh, David A; Kendall, David A; Lichtman, Aron; Chapman, Victoria

    2013-01-01

    Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies. Inhibitory cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that spinal administration of JWH133 inhibited noxious-evoked responses of spinal neurones in the model of OA pain, but not in control rats, indicating a novel spinal role of this target. We further demonstrate dynamic changes in spinal CB2 receptor mRNA and protein expression in an OA pain model. The expression of CB2 receptor protein by both neurones and microglia in the spinal cord was significantly increased in the model of OA. Hallmarks of central sensitization, significant spinal astrogliosis and increases in activity of metalloproteases MMP-2 and MMP-9 in the spinal cord were evident in the model of OA pain. Systemic administration of JWH133 attenuated these markers of central sensitization, providing a neurobiological basis for analgesic effects of the CB2 receptor in this model of OA pain. Analysis of human spinal cord revealed a negative correlation between spinal cord CB2 receptor mRNA and macroscopic knee chondropathy. These data provide new clinically relevant evidence that joint damage and spinal CB2 receptor expression are correlated combined with converging pre-clinical evidence that activation of CB2 receptors inhibits central sensitization and its contribution to the manifestation of chronic OA

  17. Relationship between mechanical sensitivity and postamputation pain: A prospective study

    DEFF Research Database (Denmark)

    Nikolajsen, Lone; IlKjær, Susanne; Jensen, Troels Staehelin

    2000-01-01

    recording of ongoing pain intensity assessed on a visual analogue scale (VAS). There was a weak but significant inverse relationship between preamputation thresholds and early stump and phantom pain. There was no relationship between preamputation thresholds and late stump and phantom pain. One week after...

  18. Reliability of four experimental mechanical pain tests in children

    DEFF Research Database (Denmark)

    Søe, Ann-Britt Langager; Thomsen, Lise L; Tornoe, Birte;

    2013-01-01

    In order to study pain in children, it is necessary to determine whether pain measurement tools used in adults are reliable measurements in children. The aim of this study was to explore the intrasession reliability of pressure pain thresholds (PPT) in healthy children. Furthermore, the aim was a...

  19. Systematic mechanism-orientated approach to chronic pancreatitis pain

    NARCIS (Netherlands)

    Bouwense, S.A.W.; Vries, M. de; Schreuder, L.T.W.; Olesen, S.S.; Frokjaer, J.B.; Drewes, A.M.; Goor, H. van; Wilder-Smith, O.H.G.

    2015-01-01

    Pain in chronic pancreatitis (CP) shows similarities with other visceral pain syndromes (i.e., inflammatory bowel disease and esophagitis), which should thus be managed in a similar fashion. Typical causes of CP pain include increased intrapancreatic pressure, pancreatic inflammation and pancreatic/

  20. Painful faces-induced attentional blink modulated by top-down and bottom-up mechanisms

    OpenAIRE

    2015-01-01

    Pain-related stimuli can capture attention in an automatic (bottom-up) or intentional (top-down) fashion. Previous studies have examined attentional capture by pain-related information using spatial attention paradigms that involve mainly a bottom-up mechanism. In the current study, we investigated the pain information–induced attentional blink (AB) using a rapid serial visual presentation (RSVP) task, and compared the effects of task-irrelevant and task-relevant pain distractors. Relationshi...

  1. Painful faces-induced attentional blink modulated by top–down and bottom–up mechanisms

    OpenAIRE

    2015-01-01

    Pain-related stimuli can capture attention in an automatic (bottom–up) or intentional (top–down) fashion. Previous studies have examined attentional capture by pain-related information using spatial attention paradigms that involve mainly a bottom–up mechanism. In the current study, we investigated the pain information-induced attentional blink (AB) using a rapid serial visual presentation (RSVP) task, and compared the effects of task-irrelevant and task-relevant pain distractors. Relationshi...

  2. Axial low back pain: one painful area--many perceptions and mechanisms.

    Directory of Open Access Journals (Sweden)

    Matti Förster

    Full Text Available Axial low back pain can be considered as a syndrome with both nociceptive and neuropathic pain components (mixed-pain. Especially neuropathic pain comprises a therapeutic challenge in practical experience and may explain why pharmacotherapy in back pain is often disappointing for both the patient and the therapist. This survey uses epidemiological and clinical data on the symptomatology of 1083 patients with axial low back pain from a cross sectional survey (painDETECT. Objectives were (1 to estimate whether neuropathic pain contributes to axial low back pain and if so to what extent. (2 To detect subgroups of patients with typical sensory symptom profiles and to analyse their demographic data and co-morbidities. (3 To compare patients with and without prior intervertebral disc surgery (IVD. Neuropathic pain components could be detected in 12% of the entire cohort. Cluster analyses of these patients revealed five distinct subgroups of patients showing a characteristic sensory profile, i.e. a typical constellation and combination of symptoms. All subgroups occurred in relevant numbers and some showed distinct neuropathic characteristics while others showed nociceptive features. Post-IVD-surgery patients showed a tendency to score more "neuropathic" than patients without surgery (not statistically significant. Axial low back pain has a high prevalence of co-morbidities with implication on therapeutic aspects. From these data it can be concluded that sensory profiles based on descriptor severity may serve as a better predictor for therapy assessment than pain intensity or sole diagnosis alone. Standardized phenotyping of pain symptoms with easy tools may help to develop an individualized therapy leading to a higher success rate in pharmacotherapy of axial low back pain.

  3. Abdominal pain in Irritable Bowel Syndrome: a review of putative psychological, neural and neuro-immune mechanisms.

    Science.gov (United States)

    Elsenbruch, Sigrid

    2011-03-01

    Chronic abdominal pain is a common symptom of great clinical significance in several areas of medicine. In many cases no organic cause can be established resulting in the classification as functional gastrointestinal disorder. Irritable Bowel Syndrome (IBS) is the most common of these conditions and is considered an important public health problem because it can be disabling and constitutes a major social and economic burden given the lack of effective treatments. IBS aetiology is most likely multi-factorial involving biological, psychological and social factors. Visceral hyperalgesia (or hypersensitivity) and visceral hypervigilance, which could be mediated by peripheral, spinal, and/or central pathways, constitute key concepts in current research on pathophysiological mechanisms of visceral hyperalgesia. The role of central nervous system mechanisms along the "brain-gut axis" is increasingly appreciated, owing to accumulating evidence from brain imaging studies that neural processing of visceral stimuli is altered in IBS together with long-standing knowledge regarding the contribution of stress and negative emotions to symptom frequency and severity. At the same time, there is also growing evidence suggesting that peripheral immune mechanisms and disturbed neuro-immune communication could play a role in the pathophysiology of visceral hyperalgesia. This review presents recent advances in research on the pathophysiology of visceral hyperalgesia in IBS, with a focus on the role of stress and anxiety in central and peripheral response to visceral pain stimuli. Together, these findings support that in addition to lower pain thresholds displayed by a significant proportion of patients, the evaluation of pain appears to be altered in IBS. This may be attributable to affective disturbances, negative emotions in anticipation of or during visceral stimulation, and altered pain-related expectations and learning processes. Disturbed "top-down" emotional and cognitive pain

  4. Pain hypersensitivity in congenital blindness is associated with faster central processing of C-fibre input

    DEFF Research Database (Denmark)

    Slimani, H.; Plaghki, L.; Ptito, M.

    2016-01-01

    Background We have recently shown that visual deprivation from birth exacerbates responses to painful thermal stimuli. However, the mechanisms underlying pain hypersensitivity in congenital blindness are unclear. Methods To study the contribution of Aδ- and C-fibres in pain perception, we measured...... thresholds and response times to selective C- and Aδ-fibre activation in congenitally blind, late blind and normally sighted participants. Ultrafast constant-temperature heat pulses were delivered to the hand with a CO2 laser using an interleaved adaptive double staircase procedure. Participants were...... instructed to respond as quickly as possible when detecting a laser-induced sensation. We used a 650 ms cut-off criterion to distinguish fast Aδ- from slow C-fibre–mediated sensations. Results Congenitally blind participants showed significantly faster reaction times to C- but not to Aδ...

  5. Painful faces-induced attentional blink modulated by top-down and bottom-up mechanisms

    Directory of Open Access Journals (Sweden)

    Chun eZheng

    2015-06-01

    Full Text Available Pain-related stimuli can capture attention in an automatic (bottom-up or intentional (top-down fashion. Previous studies have examined attentional capture by pain-related information using spatial attention paradigms that involve mainly a bottom-up mechanism. In the current study, we investigated the pain information–induced attentional blink (AB using a rapid serial visual presentation (RSVP task, and compared the effects of task-irrelevant and task-relevant pain distractors. Relationships between accuracy of target identification and individual traits (i.e., empathy and catastrophizing thinking about pain were also examined. The results demonstrated that task-relevant painful faces had a significant pain information–induced AB effect, whereas task-irrelevant faces a near-significant trend of this effect, supporting the notion that pain-related stimuli can influence the temporal dynamics of attention. Furthermore, we found a significant negative correlation between response accuracy and pain catastrophizing score in task-relevant trials. These findings suggest that active scanning of environmental information related to pain produces greater deficits in cognition than does unintentional attention toward pain, which may represent the different ways in which healthy individuals and patients with chronic pain process pain-relevant information. These results may provide insight into the understanding of maladaptive attentional processing in patients with chronic pain.

  6. Painful faces-induced attentional blink modulated by top–down and bottom–up mechanisms

    Science.gov (United States)

    Zheng, Chun; Wang, Jin-Yan; Luo, Fei

    2015-01-01

    Pain-related stimuli can capture attention in an automatic (bottom–up) or intentional (top–down) fashion. Previous studies have examined attentional capture by pain-related information using spatial attention paradigms that involve mainly a bottom–up mechanism. In the current study, we investigated the pain information-induced attentional blink (AB) using a rapid serial visual presentation (RSVP) task, and compared the effects of task-irrelevant and task-relevant pain distractors. Relationships between accuracy of target identification and individual traits (i.e., empathy and catastrophizing thinking about pain) were also examined. The results demonstrated that task-relevant painful faces had a significant pain information-induced AB effect, whereas task-irrelevant faces showed a near-significant trend of this effect, supporting the notion that pain-related stimuli can influence the temporal dynamics of attention. Furthermore, we found a significant negative correlation between response accuracy and pain catastrophizing score in task-relevant trials. These findings suggest that active scanning of environmental information related to pain produces greater deficits in cognition than does unintentional attention toward pain, which may represent the different ways in which healthy individuals and patients with chronic pain process pain-relevant information. These results may provide insight into the understanding of maladaptive attentional processing in patients with chronic pain. PMID:26082731

  7. Painful faces-induced attentional blink modulated by top-down and bottom-up mechanisms.

    Science.gov (United States)

    Zheng, Chun; Wang, Jin-Yan; Luo, Fei

    2015-01-01

    Pain-related stimuli can capture attention in an automatic (bottom-up) or intentional (top-down) fashion. Previous studies have examined attentional capture by pain-related information using spatial attention paradigms that involve mainly a bottom-up mechanism. In the current study, we investigated the pain information-induced attentional blink (AB) using a rapid serial visual presentation (RSVP) task, and compared the effects of task-irrelevant and task-relevant pain distractors. Relationships between accuracy of target identification and individual traits (i.e., empathy and catastrophizing thinking about pain) were also examined. The results demonstrated that task-relevant painful faces had a significant pain information-induced AB effect, whereas task-irrelevant faces showed a near-significant trend of this effect, supporting the notion that pain-related stimuli can influence the temporal dynamics of attention. Furthermore, we found a significant negative correlation between response accuracy and pain catastrophizing score in task-relevant trials. These findings suggest that active scanning of environmental information related to pain produces greater deficits in cognition than does unintentional attention toward pain, which may represent the different ways in which healthy individuals and patients with chronic pain process pain-relevant information. These results may provide insight into the understanding of maladaptive attentional processing in patients with chronic pain.

  8. Pain-related mediators underlie incision-induced mechanical nociception in the dorsal root ganglia

    Institute of Scientific and Technical Information of China (English)

    Xiuhong Yuan; Xiangyan Liu; Qiuping Tang; Yunlong Deng

    2013-01-01

    Approximately 50-70% of patients experience incision-induced mechanical nociception after sur-gery. However, the mechanism underlying incision-induced mechanical nociception is stil unclear. Interleukin-10 and brain-derived neurotrophic factor are important pain mediators, but whether in-terleukin-10 and brain-derived neurotrophic factor are involved in incision-induced mechanical no-ciception remains uncertain. In this study, forty rats were divided randomly into the incision surgery (n=32) and sham surgery (n=8) groups. Plantar incision on the central part of left hind paw was performed under anesthesia in rats from the surgery group. Rats in the sham surgery group re-ceived anesthesia, but not an incision. Von Frey test results showed that, compared with the sham surgery group, incision surgery decreased the withdrawal threshold of rats at 0.5, 3, 6 and 24 hours after incision. Immunofluorescence staining in the dorsal root ganglia of the spinal cord (L 3-5 ) showed that interleukin-10 and brain-derived neurotrophic factor were expressed mainly on smal-and medium-sized neurons (diameter40μm) at 6 and 24 hours after incision surgery, which corresponded to the decreased mechanical withdrawal threshold of rats in the surgery group. These experimental findings suggest that expression pattern shift of interleukin-10 and brain-derived neurotrophic factor induced by inci-sion surgery in dorsal root ganglia of rats was closely involved in lowering the threshold to me-chanical stimulus in the hind paw fol owing incision surgery. Pain-related mediators induced by in-cision surgery in dorsal root ganglia of rats possibly underlie mechanical nociception in ipsilateral hind paws.

  9. Targeting Epigenetic Mechanisms for Chronic Pain: A Valid Approach for the Development of Novel Therapeutics.

    Science.gov (United States)

    Ligon, Casey O; Moloney, Rachel D; Greenwood-Van Meerveld, Beverley

    2016-04-01

    Chronic pain is a multifaceted and complex condition. Broadly classified into somatic, visceral, or neuropathic pain, it is poorly managed despite its prevalence. Current drugs used for the treatment of chronic pain are limited by tolerance with long-term use, abuse potential, and multiple adverse side effects. The persistent nature of pain suggests that epigenetic machinery may be a critical factor driving chronic pain. In this review, we discuss the latest insights into epigenetic processes, including DNA methylation, histone modifications, and microRNAs, and we describe their involvement in the pathophysiology of chronic pain and whether epigenetic modifications could be applied as future therapeutic targets for chronic pain. We provide evidence from experimental models and translational research in human tissue that have enhanced our understanding of epigenetic processes mediating nociception, and we then speculate on the potential future use of more specific and selective agents that target epigenetic mechanisms to attenuate pain.

  10. Participation of central GABAA receptors in the trigeminal processing of mechanical allodynia in rats

    Science.gov (United States)

    Kim, Min Ji; Park, Young Hong; Yang, Kui Ye; Ju, Jin Sook; Bae, Yong Chul

    2017-01-01

    Here we investigated the central processing mechanisms of mechanical allodynia and found a direct excitatory link with low-threshold input to nociceptive neurons. Experiments were performed on male Sprague-Dawley rats weighing 230-280 g. Subcutaneous injection of interleukin 1 beta (IL-1β) (1 ng/10 µL) was used to produce mechanical allodynia and thermal hyperalgesia. Intracisternal administration of bicuculline, a gamma aminobutyric acid A (GABAA) receptor antagonist, produced mechanical allodynia in the orofacial area under normal conditions. However, intracisternal administration of bicuculline (50 ng) produced a paradoxical anti-allodynic effect under inflammatory pain conditions. Pretreatment with resiniferatoxin (RTX), which depletes capsaicin receptor protein in primary afferent fibers, did not alter the paradoxical anti-allodynic effects produced by the intracisternal injection of bicuculline. Intracisternal injection of bumetanide, an Na-K-Cl cotransporter (NKCC 1) inhibitor, reversed the IL-1β-induced mechanical allodynia. In the control group, application of GABA (100 µM) or muscimol (3 µM) led to membrane hyperpolarization in gramicidin perforated current clamp mode. However, in some neurons, application of GABA or muscimol led to membrane depolarization in the IL-1β-treated rats. These results suggest that some large myelinated Aβ fibers gain access to the nociceptive system and elicit pain sensation via GABAA receptors under inflammatory pain conditions. PMID:28066142

  11. Fabrication and mechanical performance of the ATLAS central solenoid

    CERN Document Server

    Mizumaki, S; Kobayashi, T; Yamaoka, H; Kondo, Y; Kawai, M; Doi, Y; Haruyama, T; Mine, S; Takano, H; Yamamoto, A; Kondo, T; ten Kate, H H J

    2002-01-01

    Fabrication of the central solenoid for ATLAS detector in the CERN- LHC project was completed, and the performance test has been successfully carried out in Japan. The solenoid has arrived at CERN to be assembled with the LAr calorimeter. This paper describes the fabrication and mechanical, performance of the ATLAS central solenoid. (10 refs).

  12. Cannabinoids and centrak neuropathic pain. A review (Cannabinoidi e dolore neuropatico centrale. Una rassegna

    Directory of Open Access Journals (Sweden)

    Francesco Crestani

    2014-03-01

    Full Text Available Only recently, the medical community highlighted the pharmacological scientific bases of the effects of Cannabis. The most important active principle, Delta-9-tetrahydrocannabinol was identified in the second half of the last century, and receptors were subsequently identified and endogenous ligands, called endocannabinoids, were characterized. The effectiveness of the cannabinoids in the treatment of nausea and vomit due to anti-neoplastic chemotherapy and in the wasting-syndrome during AIDS is recognized. Moreover, the cannabinoids have shown analgesic properties, particularly interesting with regard to the central neuropathic pain. This article will review the current knowledge and will give practical guidance on how to proceed in prescribing cannabinoids.

  13. Chronic whiplash and central sensitization; an evaluation of the role of a myofascial trigger points in pain modulation

    Directory of Open Access Journals (Sweden)

    Freeman Michael D

    2009-04-01

    Full Text Available Abstract Objective it has been established that chronic neck pain following whiplash is associated with the phenomenon of central sensitization, in which injured and uninjured parts of the body exhibit lowered pain thresholds due to an alteration in central pain processing. it has furthermore been hypothesized that peripheral sources of nociception in the muscles may perpetuate central sensitization in chronic whiplash. the hypothesis explored in the present study was whether myofascial trigger points serve as a modulator of central sensitization in subjects with chronic neck pain. Design controlled case series. Setting outpatient chronic pain clinic. Subjects seventeen patients with chronic and intractable neck pain and 10 healthy controls without complaints of neck pain. Intervention symptomatic subjects received anesthetic infiltration of myofascial trigger points in the upper trapezius muscles and controls received the anesthetic in the thigh. Outcome measures: pre and post injection cervical range of motion, pressure pain thresholds (ppt over the infraspinatus, wrist extensor, and tibialis anterior muscles. sensitivity to light (photophobia and subjects' perception of pain using a visual analog scale (vas were also evaluated before and after injections. only the ppt was evaluated in the asymptomatic controls. Results immediate (within 1 minute alterations in cervical range of motion and pressure pain thresholds were observed following an average of 3.8 injections with 1–2 cc of 1% lidocaine into carefully identified trigger points. cervical range of motion increased by an average of 49% (p = 0.000 in flexion and 44% (p = 0.001 in extension, 47% (p = 0.000 and 28% (p Conclusion the present data suggest that myofascial trigger points serve to perpetuate lowered pain thresholds in uninjured tissues. additionally, it appears that lowered pain thresholds associated with central sensitization can be immediately reversed, even when associated

  14. Chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala.

    Science.gov (United States)

    Li, Ming-Jia; Liu, Ling-Yu; Chen, Lin; Cai, Jie; Wan, You; Xing, Guo-Gang

    2017-04-01

    Exacerbation of pain by chronic stress and comorbidity of pain with stress-related psychiatric disorders, including anxiety and depression, represent significant clinical challenges. However, the underlying mechanisms still remain unclear. Here, we investigated whether chronic forced swim stress (CFSS)-induced exacerbation of neuropathic pain is mediated by the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala (CeA). We first demonstrated that CFSS indeed produces both depressive-like behaviors and exacerbation of spared nerve injury (SNI)-induced mechanical allodynia in rats. Moreover, we revealed that CFSS induces both sensitization of basolateral amygdala (BLA) neurons and augmentation of long-term potentiation (LTP) at the BLA-CeA synapse and meanwhile, exaggerates both SNI-induced sensitization of CeA neurons and LTP at the parabrachial (PB)-CeA synapse. In addition, we discovered that CFSS elevates SNI-induced functional up-regulation of GluN2B-containing NMDA (GluN2B-NMDA) receptors in the CeA, which is proved to be necessary for CFSS-induced augmentation of LTP at the PB-CeA synapse and exacerbation of pain hypersensitivity in SNI rats. Suppression of CFSS-elicited depressive-like behaviors by antidepressants imipramine or ifenprodil inhibits the CFSS-induced exacerbation of neuropathic pain. Collectively, our findings suggest that CFSS potentiates synaptic efficiency of the BLA-CeA pathway, leading to the activation of GluN2B-NMDA receptors and sensitization of CeA neurons, which subsequently facilitate pain-related synaptic plasticity of the PB-CeA pathway, thereby exacerbating SNI-induced neuropathic pain. We conclude that chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the CeA.

  15. The race to the nociceptor: mechanical versus temperature effects in thermal pain of dental neurons

    Science.gov (United States)

    Lin, Min; Liu, Fusheng; Liu, Shaobao; Ji, Changchun; Li, Ang; Lu, Tian Jian; Xu, Feng

    2017-03-01

    The sensing of hot and cold stimuli by dental neurons differs in several fundamental ways. These sensations have been characterized quantitatively through the measured time course of neural discharge signals that result from hot or cold stimuli applied to the teeth of animal models. Although various hypotheses have been proposed to explain the underlying mechanism, the ability to test competing hypotheses against experimental recorded data using biophysical models has been hindered by limitations in our understanding of the specific ion channels involved in nociception of dental neurons. Here we apply recent advances in established biophysical models to test the competing hypotheses. We show that a sharp shooting pain sensation experienced shortly following cold stimulation cannot be attributed to the activation of thermosensitive ion channels, thereby falsifying the so-called neuronal hypothesis, which states that rapidly transduced sensations of coldness are related to thermosensitive ion channels. Our results support a central role of mechanosensitive ion channels and the associated hydrodynamic hypothesis. In addition to the hydrodynamic hypothesis, we also demonstrate that the long time delay of dental neuron responses after hot stimulation could be attributed to the neuronal hypothesis—that a relatively long time is required for the temperature around nociceptors to reach some threshold. The results are useful as a model of how multiphysical phenomena can be combined to provide mechanistic insight into different mechanisms underlying pain sensations.

  16. Persistent facial pain conditions

    DEFF Research Database (Denmark)

    Forssell, Heli; Alstergren, Per; Bakke, Merete;

    2016-01-01

    , clinical features, consequences, central and peripheral mechanisms, diagnostic criteria (DC/TMD), and principles of management. For each of the neuropathic facial pain entities, the definitions, prevalence, clinical features, and diagnostics are described. The current understanding of the pathophysiology...

  17. Short Term Effects of Mobilization Techniques on Neck Pain and Deep Neck Flexor Muscle Endurance in Patients with Mechanical Chronic Neck Pain

    OpenAIRE

    Kılınç, Hasan Erkan; Harput, Gülcan; Baltacı, Gül; İnce, Deniz İnal

    2014-01-01

    Objectives: The aim of the study was to investigate short term effects of cervical and scapular mobilization techniques on neck pain and deep cervical muscles endurance in chronical mechanical neck pain patients. Methods: 22 chronical mechanic neck pain patients four male 18 female (mean age: mean±sd 35.59± 15.85) were included. Before treatment, neck pain level (visual analog scale) and deep neck flexor muscles endurance (in supine position with digital chronometer) of all patients were eval...

  18. Segmental hypersensitivity and spinothalamic function in spinal cord injury pain

    DEFF Research Database (Denmark)

    Finnerup, Nanna Brix; Sørensen, Leif Hougaard; Biering-Sørensen, Fin;

    2007-01-01

    The mechanisms underlying central pain following spinal cord injury (SCI) are unsettled. The purpose of the present study was to examine differences in spinothalamic tract function below injury level and evoked pain in incomplete SCI patients with neuropathic pain below injury level (central pain...

  19. Effects of Electroacupuncture on Pain Threshold of Laboring Rats and the Expression of Norepinephrine Transporter and α2 Adrenergic Receptor in the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Qianli Tang

    2016-01-01

    Full Text Available To observe the effects of electroacupuncture on pain threshold of laboring rats and the expression of norepinephrine transporter and α2 adrenergic receptor in the central nervous system to determine the mechanism of the analgesic effect of labor. 120 pregnant rats were divided into 6 groups: a control group, 4 electroacupuncture groups, and a meperidine group. After interventions, the warm water tail-flick test was used to observe pain threshold. NE levels in serum, NET, and α2AR mRNA and protein expression levels in the central nervous system were measured. No difference in pain threshold was observed between the 6 groups before intervention. After intervention, increased pain thresholds were observed in all groups except the control group with a higher threshold seen in the electroacupuncture groups. Serum NE levels decreased in the electroacupuncture and MP groups. Increases in NET and α2AR expression in the cerebral cortex and decreases in enlarged segments of the spinal cord were seen. Acupuncture increases uptake of NE via cerebral NET and decreases its uptake by spinal NET. The levels of α2AR are also increased and decreased, respectively, in both tissues. This results in a decrease in systemic NE levels and may be the mechanism for its analgesic effects.

  20. Prevention of NKCC1 phosphorylation avoids downregulation of KCC2 in central sensory pathways and reduces neuropathic pain after peripheral nerve injury.

    Science.gov (United States)

    Mòdol, Laura; Cobianchi, Stefano; Navarro, Xavier

    2014-08-01

    Neuropathic pain after peripheral nerve injury is characterized by loss of inhibition in both peripheral and central pain pathways. In the adult nervous system, the Na(+)-K(+)-2Cl(-) (NKCC1) and neuron-specific K(+)-Cl(-) (KCC2) cotransporters are involved in setting the strength and polarity of GABAergic/glycinergic transmission. After nerve injury, the balance between these cotransporters changes, leading to a decrease in the inhibitory tone. However, the role that NKCC1 and KCC2 play in pain-processing brain areas is unknown. Our goal was to study the effects of peripheral nerve injury on NKCC1 and KCC2 expression in dorsal root ganglia (DRG), spinal cord, ventral posterolateral (VPL) nucleus of the thalamus, and primary somatosensory (S1) cortex. After sciatic nerve section and suture in adult rats, assessment of mechanical and thermal pain thresholds showed evidence of hyperalgesia during the following 2 months. We also found an increase in NKCC1 expression in the DRG and a downregulation of KCC2 in spinal cord after injury, accompanied by later decrease of KCC2 levels in higher projection areas (VPL and S1) from 2 weeks postinjury, correlating with neuropathic pain signs. Administration of bumetanide (30 mg/kg) during 2 weeks following sciatic nerve lesion prevented the previously observed changes in the spinothalamic tract projecting areas and the appearance of hyperalgesia. In conclusion, the present results indicate that changes in NKCC1 and KCC2 in DRG, spinal cord, and central pain areas may contribute to development of neuropathic pain.

  1. The Correlation Between Neurologic Findings And DXA in Mechanical Low Back Pain and/or Leg Pain

    Directory of Open Access Journals (Sweden)

    Halil Koyuncu

    2012-04-01

    Full Text Available Aim: Mechanical problems are frequently encountered and may cause low back pain (LBP and leg pain by pressure on nerve roots. Neurologic findings like decreased deep tendon reflexes may be found during the physical examination. There are many etiologic factors in the pathogenesis of LBP and metabolic bone diseases like osteoporosis and osteomalacia also may cause mecanical LBP. Materials and Methods: In this study, 25 patients between 30-65 years were evaluated. In the patients, sensorial changes, deep tendon reflexes and muscle strength were correlated with dual x-ray absorbsiometry (DXA results. Demographic findings (age, sex, occupation, education and clinical results (pain duration, pain severity, height, weight were evaluated. In DXA evaluation, L1-L4 total, femur neck and femur total bone mineral density (BMD and T-scores were reported. Results: Pain severity, according to visual analog scale (VAS was higher than six. Muscle strength, sensation and deep tendon reflex averages were found to be normal. DXA results were found to be osteopenic in femoral neck region of our patients. DXA results and clinical findings showed a weak and negative statistically significant correlation only between BMD at L1-L4 and pain severity. Conclusion: This study should be performed comparatively, multicenter, in a larger number of patients with LBP, for a longer period of follow-up. (Turkish Journal of Osteoporosis 2012;18:19-23

  2. Tetrahydrocannabinol (Delta 9-THC Treatment in Chronic Central Neuropathic Pain and Fibromyalgia Patients: Results of a Multicenter Survey

    Directory of Open Access Journals (Sweden)

    Janet Weber

    2009-01-01

    Full Text Available Central neuropathic pain is difficult to treat, but delta 9-Tetrahydrocannabinol (delta 9-THC may be a promising therapeutic agent. We administered in 172 patients on average 7.5 mg delta 9-THC over 7 months. Of these, 48 patients prematurely withdrew due to side effects, insufficient analgesia, or expense of therapy. Thus, 124 patients were assessed retrospectively in a multicenter telephone survey. Reported changes in pain intensity, recorded on a numeric rating scale (NRS, Pain Disability Index (PDI, Medical Outcomes Short-Form (SF-12, Quality of Life Impairment by Pain (QLIP, Hospital Anxiety Depression Scale (HADS, and amount of concomitant pain medication were recorded. Psychometric parameters (PDI, SF-12, QLIP, HADS and pain intensity improved significantly during delta 9-THC treatment. Opioid doses were reduced and patients perceived THC therapy as effective with tolerable side effects. About 25% of the patients, however, did not tolerate the treatment. Therapy success and tolerance can be assessed by a transient delta 9-THC titration and its maintained administration for several weeks. The present survey demonstrates its ameliorating potential for the treatment of chronic pain in central neuropathy and fibromyalgia. A supplemental delta 9-THC treatment as part of a broader pain management plan therefore may represent a promising coanalgesic therapeutic option.

  3. Pain mechanisms and ultrasonic inflammatory activity as prognostic factors in patients with psoriatic arthritis: protocol for a prospective, exploratory cohort study

    Science.gov (United States)

    Dreyer, Lene; Mease, Philip; de Wit, Maarten; Skov, Lone; Glintborg, Bente; Christensen, Anton Wulf; Ballegaard, Christine; Bliddal, Henning; Bukhave, Kristine; Bartels, Else Marie; Amris, Kirstine; Ellegaard, Karen; Kristensen, Lars Erik

    2016-01-01

    Introduction Persistent pain is a major concern for patients with psoriatic arthritis (PsA). Pain may be due to inflammatory activity or augmented central pain processing. Unawareness of the origin and mechanisms of pain can lead to misinterpretation of disease activity (by composite scores) and erroneous treatments. Ultrasonography (US) is a highly sensitive method to detect tissue inflammation. Evaluating pain mechanisms in relation to US measures may prove valuable in predicting response to treatment in PsA. Aims To study the association and prognostic value of pain mechanisms, ultrasonic activity and clinical outcomes in patients with PsA who intensify antirheumatic treatment. Methods and analyses 100 participants >18 years of age with PsA who initiate or switch antirheumatic treatment (biologicals and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs)) will be prospectively recruited from outpatient clinics in Copenhagen. All data (demographics, clinical, imaging, blood samples and patient-reported outcomes) will be collected at baseline and after 4 months. Pain is assessed by the PainDETECT Questionnaire, Visual Analogue Scale for pain, Swollen to Tender Joint Count Ratio, Widespread Pain Index and tender point examination. The association between pain variables and clinical/US characteristics will be described by correlation analyses. The predictive value of pain measures and baseline US scores on treatment response will be analysed with regression models. Outcomes are composite and clinical, as well as patient reported. Ethics and dissemination The study is approved by the ethics committee of the Capital Region of Denmark (H-15009080) and has been designed in cooperation with patient research partners. The study is registered at clinicaltrials.gov (number NCT02572700). Results will be disseminated through publication in international peer-reviewed journals. Trial registration number NCT02572700, Pre-results. PMID:27084281

  4. Brain stimulation therapy for central post-stroke pain from a perspective of interhemispheric neural network remodeling

    Directory of Open Access Journals (Sweden)

    Takashi eMorishita

    2016-04-01

    Full Text Available Central post-stroke pain (CPSP is a debilitating, severe disorder affecting patient quality of life. Since CPSP is refractory to medication, various treatment modalities have been tried with marginal results. Following the first report of epidural motor cortex stimulation (MCS for CPSP, many researchers have investigated the mechanisms of electrical stimulation of the motor cortex. CPSP is currently considered to be a maladapted network reorganization problem following stroke, and recent studies have revealed that the activities of the impaired hemisphere after stroke may be inhibited by the contralesional hemisphere. Even though this interhemispheric inhibition (IHI theory was originally proposed to explain the motor recovery process in stroke patients, we considered that IHI may also contribute to the CPSP mechanism. Based on the IHI theory and the fact that electrical stimulation of the motor cortex suppresses CPSP, we hypothesized that the inhibitory signals from the contralesional hemisphere may suppress the activities of the motor cortex in the ipsilesional hemisphere, and therefore pain suppression mechanisms may be malfunctioning in CPSP patients. In this context, transcranial direct current stimulation (tDCS was considered to be a reasonable procedure to address the interhemispheric imbalance, as the bilateral motor cortex can be simultaneously stimulated using an anode (excitatory and cathode (inhibitory. In this paper, we review the potential mechanisms and propose a new model of CPSP. We also report two cases where CPSP was addressed with transcranial direct current stimulation (tDCS, discuss the potential roles of tDCS in the treatment of CPSP, and make recommendations for future studies.

  5. Brain Stimulation Therapy for Central Post-Stroke Pain from a Perspective of Interhemispheric Neural Network Remodeling.

    Science.gov (United States)

    Morishita, Takashi; Inoue, Tooru

    2016-01-01

    Central post-stroke pain (CPSP) is a debilitating, severe disorder affecting patient quality of life. Since CPSP is refractory to medication, various treatment modalities have been tried with marginal results. Following the first report of epidural motor cortex (M1) stimulation (MCS) for CPSP, many researchers have investigated the mechanisms of electrical stimulation of the M1. CPSP is currently considered to be a maladapted network reorganization problem following stroke, and recent studies have revealed that the activities of the impaired hemisphere after stroke may be inhibited by the contralesional hemisphere. Even though this interhemispheric inhibition (IHI) theory was originally proposed to explain the motor recovery process in stroke patients, we considered that IHI may also contribute to the CPSP mechanism. Based on the IHI theory and the fact that electrical stimulation of the M1 suppresses CPSP, we hypothesized that the inhibitory signals from the contralesional hemisphere may suppress the activities of the M1 in the ipsilesional hemisphere, and therefore pain suppression mechanisms may be malfunctioning in CPSP patients. In this context, transcranial direct current stimulation (tDCS) was considered to be a reasonable procedure to address the interhemispheric imbalance, as the bilateral M1 can be simultaneously stimulated using an anode (excitatory) and cathode (inhibitory). In this article, we review the potential mechanisms and propose a new model of CPSP. We also report two cases where CPSP was addressed with tDCS, discuss the potential roles of tDCS in the treatment of CPSP, and make recommendations for future studies.

  6. Chronic sensory stroke with and without central pain is associated with bilaterally distributed sensory abnormalities as detected by quantitative sensory testing.

    Science.gov (United States)

    Krause, Thomas; Asseyer, Susanna; Geisler, Frederik; Fiebach, Jochen B; Oeltjenbruns, Jochen; Kopf, Andreas; Villringer, Kersten; Villringer, Arno; Jungehulsing, Gerhard J

    2016-01-01

    Approximately 20% of patients suffering from stroke with pure or predominant sensory symptoms (referred to as sensory stroke patients) develop central poststroke pain (CPSP). It is largely unknown what distinguishes these patients from those who remain pain free. Using quantitative sensory testing (QST), we analyzed the somatosensory profiles of 50 patients with chronic sensory stroke, of which 25 suffered from CPSP. As compared with reference data from healthy controls, patients with CPSP showed alterations of thermal and mechanical thresholds on the body area contralateral to their stroke (P pain sensory stroke [NPSS] patients) exhibited similar albeit less pronounced contralesional changes. Paradoxical heat sensation (PHS) and dynamic mechanical allodynia (DMA) showed higher values in CPSP, and an elevated cold detection threshold (CDT) was seen more often in CPSP than in patients with NPSS (P pain summation (wind-up ratio) each correlated with the presence of pain (P < 0.05). On the homologous ipsilesional body area, both patient groups showed additional significant abnormalities as compared with the reference data, which strongly resembled the contralesional changes. In summary, our analysis reveals that CPSP is associated with impaired temperature perception and positive sensory signs, but differences between patients with CPSP and NPSS are subtle. Both patients with CPSP and NPSS show considerable QST changes on the ipsilesional body side. These results are in part paralleled by recent findings of bilaterally spread cortical atrophy in CPSP and might reflect chronic maladaptive cortical plasticity, particularly in patients with CPSP.

  7. Transcutaneous Electrical Nerve Stimulation (TENS) reduces pain, fatigue, and hyperalgesia while restoring central inhibition in primary fibromyalgia

    OpenAIRE

    Dailey, Dana L.; Rakel, Barbara A; Vance, Carol GT; Richard E. Liebano; Anand, Amrit S; Bush, Heather M.; Lee, Kyoung S; Lee, Jennifer E.; Sluka, Kathleen A.

    2013-01-01

    Because TENS works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double-blinded randomized, placebo controlled cross-over design to test effects of a single treatment of TENS in people with fibromyalgia. Three treatments were assessed in random or...

  8. Laparoscopic Cholecystectomy for Gallbladder Calculosis in Fibromyalgia Patients: Impact on Musculoskeletal Pain, Somatic Hyperalgesia and Central Sensitization.

    Science.gov (United States)

    Costantini, Raffaele; Affaitati, Giannapia; Massimini, Francesca; Tana, Claudio; Innocenti, Paolo; Giamberardino, Maria Adele

    2016-01-01

    Fibromyalgia, a chronic syndrome of diffuse musculoskeletal pain and somatic hyperalgesia from central sensitization, is very often comorbid with visceral pain conditions. In fibromyalgia patients with gallbladder calculosis, this study assessed the short and long-term impact of laparoscopic cholecystectomy on fibromyalgia pain symptoms. Fibromyalgia pain (VAS scale) and pain thresholds in tender points and control areas (skin, subcutis and muscle) were evaluated 1week before (basis) and 1week, 1,3,6 and 12months after laparoscopic cholecystectomy in fibromyalgia patients with symptomatic calculosis (n = 31) vs calculosis patients without fibromyalgia (n. 26) and at comparable time points in fibromyalgia patients not undergoing cholecystectomy, with symptomatic (n = 27) and asymptomatic (n = 28) calculosis, and no calculosis (n = 30). At basis, fibromyalgia+symptomatic calculosis patients presented a significant linear correlation between the number of previously experienced biliary colics and fibromyalgia pain (direct) and muscle thresholds (inverse)(pfibromyalgia pain significantly increased and all thresholds significantly decreased at 1week and 1month (1-way ANOVA, pFibromyalgia pain and thresholds returned to preoperative values at 3months, then pain significantly decreased and thresholds significantly increased at 6 and 12months (pfibromyalgia patients undergoing cholecystectomy thresholds did not change; in all other fibromyalgia groups not undergoing cholecystectomy fibromyalgia pain and thresholds remained stable, except in fibromyalgia+symptomatic calculosis at 12months when pain significantly increased and muscle thresholds significantly decreased (pfibromyalgia symptoms and that laparoscopic cholecystectomy produces only a transitory worsening of these symptoms, largely compensated by the long-term improvement/desensitization due to gallbladder removal. This study provides new insights into the role of visceral pain comorbidities and the effects of

  9. Pain in Patients with Pancreatic Cancer: Prevalence, Mechanisms, Management and Future Developments.

    Science.gov (United States)

    Koulouris, Andreas I; Banim, Paul; Hart, Andrew R

    2017-04-01

    Pain affects approximately 80% of patients with pancreatic cancer, with half requiring strong opioid analgesia, namely: morphine-based drugs on step three of the WHO analgesic ladder (as opposed to the weak opioids: codeine and tramadol). The presence of pain is associated with reduced survival. This article reviews the literature regarding pain: prevalence, mechanisms, pharmacological, and endoscopic treatments and identifies areas for research to develop individualized patient pain management pathways. The online literature review was conducted through: PubMed, Clinical Key, Uptodate, and NICE Evidence. There are two principal mechanisms for pain: pancreatic duct obstruction and pancreatic neuropathy which, respectively, activate mechanical and chemical nociceptors. In pancreatic neuropathy, several histological, molecular, and immunological changes occur which correlate with pain including: transient receptor potential cation channel activation and mast cell infiltration. Current pain management is empirical rather etiology-based and is informed by the WHO analgesic ladder for first-line therapies, and then endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in patients with resistant pain. For EUS-CPN, there is only one clinical trial reporting a benefit, which has limited generalizability. Case series report pancreatic duct stenting gives effective analgesia, but there are no clinical trials. Progress in understanding the mechanisms for pain and when this occurs in the natural history, together with assessing new therapies both pharmacological and endoscopic, will enable individualized care and may improve patients' quality of life and survival.

  10. Understanding Central Mechanisms of Acupuncture Analgesia Using Dynamic Quantitative Sensory Testing: A Review

    Directory of Open Access Journals (Sweden)

    Jiang-Ti Kong

    2013-01-01

    Full Text Available We discuss the emerging translational tools for the study of acupuncture analgesia with a focus on psychophysical methods. The gap between animal mechanistic studies and human clinical trials of acupuncture analgesia calls for effective translational tools that bridge neurophysiological data with meaningful clinical outcomes. Temporal summation (TS and conditioned pain modulation (CPM are two promising tools yet to be widely utilized. These psychophysical measures capture the state of the ascending facilitation and the descending inhibition of nociceptive transmission, respectively. We review the basic concepts and current methodologies underlying these measures in clinical pain research, and illustrate their application to research on acupuncture analgesia. Finally, we highlight the strengths and limitations of these research methods and make recommendations on future directions. The appropriate addition of TS and CPM to our current research armamentarium will facilitate our efforts to elucidate the central analgesic mechanisms of acupuncture in clinical populations.

  11. Balancing "hands-on" with "hands-off" physical therapy interventions for the treatment of central sensitization pain in osteoarthritis.

    Science.gov (United States)

    Lluch Girbés, E; Meeus, M; Baert, I; Nijs, J

    2015-04-01

    Traditional understanding of osteoarthritis-related pain has recently been challenged in light of evidence supporting a key role of central sensitization in a subgroup of this population. This fact may erroneously lead musculoskeletal therapists to conclude that hands-on interventions have no place in OA management, and that hands-off interventions must be applied exclusively. The aim of this paper is to encourage clinicians in finding an equilibrium between hands-on and hands-off interventions in patients with osteoarthritis-related pain dominated by central sensitization. The theoretical rationale for simultaneous application of manual therapy and pain neuroscience education is presented. Practical problems when combining these interventions are also addressed. Future studies should explore the combined effects of these treatment strategies to examine whether they increase therapeutic outcomes against current approaches for chronic osteoarthritis-related pain.

  12. Conservative management of uncomplicated mechanical neck pain in a military aviator

    OpenAIRE

    2010-01-01

    Non-radicular neck pain arising from local musculoskeletal structures, known as mechanical neck pain or somatic dysfunction, is highly prevalent in the fighter jet aviator population. The management of this problem includes both therapeutic and aeromedical decisions. In addition to non-steroidal anti-inflammatory medications, waiver guides recommend therapeutic exercise and manipulative therapy as treatments for somatic spine pain in aviators, and such treatments are employed in many military...

  13. Conservative Management of Uncomplicated Mechanical Neck Pain in a Military Aviator

    Science.gov (United States)

    2010-01-01

    on-station osteopath, chiropractor , or physical therapist who is trained in these procedures. While the management of mechanical neck pain in the...Reference and Waiver Guide states that neck and back pain from biomechan- ical derangements of the spine and resulting muscle aches and spasms, known...use of fl ight surgeon pre- scribed NSAIDs for a short-term course of care to manage back or neck pain .6,7 These medications are considered

  14. Reliability of four experimental mechanical pain tests in children

    Directory of Open Access Journals (Sweden)

    Soee AL

    2013-02-01

    Full Text Available Ann-Britt L Soee,1 Lise L Thomsen,2 Birte Tornoe,1,3 Liselotte Skov11Department of Pediatrics, Children’s Headache Clinic, Copenhagen University Hospital Herlev, Copenhagen, Denmark; 2Department of Neuropediatrics, Juliane Marie Centre, Copenhagen University Hospital Rigshospitalet, København Ø, Denmark; 3Department of Physiotherapy, Medical Department O, Copenhagen University Hospital Herlev, Herlev, DenmarkPurpose: In order to study pain in children, it is necessary to determine whether pain measurement tools used in adults are reliable measurements in children. The aim of this study was to explore the intrasession reliability of pressure pain thresholds (PPT in healthy children. Furthermore, the aim was also to study the intersession reliability of the following four tests: (1 Total Tenderness Score; (2 PPT; (3 Visual Analog Scale score at suprapressure pain threshold; and (4 area under the curve (stimulus–response functions for pressure versus pain.Participants and methods: Twenty-five healthy school children, 8–14 years of age, participated. Test 2, PPT, was repeated three times at 2 minute intervals on the same day to estimate PPT intrasession reliability using Cronbach’s alpha. Tests 1–4 were repeated after median 21 (interquartile range 10.5–22 days, and Pearson’s correlation coefficient was used to describe the intersession reliability.Results: The PPT test was precise and reliable (Cronbach’s alpha ≥ 0.92. All tests showed a good to excellent correlation between days (intersessions r = 0.66–0.81. There were no indications of significant systematic differences found in any of the four tests between days.Conclusion: All tests seemed to be reliable measurements in pain evaluation in healthy children aged 8–14 years. Given the small sample size, this conclusion needs to be confirmed in future studies.Keywords: repeatability, intraindividual reliability, pressure pain threshold, pain measurement, algometer

  15. Mechanisms and Management of Diabetic Painful Distal Symmetrical Polyneuropathy

    OpenAIRE

    Tesfaye, Solomon; Boulton, Andrew J.M.; Dickenson, Anthony H

    2013-01-01

    Although a number of the diabetic neuropathies may result in painful symptomatology, this review focuses on the most common: chronic sensorimotor distal symmetrical polyneuropathy (DSPN). It is estimated that 15–20% of diabetic patients may have painful DSPN, but not all of these will require therapy. In practice, the diagnosis of DSPN is a clinical one, whereas for longitudinal studies and clinical trials, quantitative sensory testing and electrophysiological assessment are usually necessary...

  16. Neural Mechanisms of Temporomandibular Joint and Masticatory Muscle Pain: A Possible Role for Peripheral Glutamate Receptor Mechanisms

    Directory of Open Access Journals (Sweden)

    David K Lam

    2005-01-01

    Full Text Available The purpose of the present review is to correlate recent knowledge of the role of peripheral ionotropic glutamate receptors in the temporomandibular joint and muscle pain from animal and human experimental pain models with findings in patients. Chronic pain is common, and many people suffer from chronic pain conditions involving deep craniofacial tissues such as temporomandibular disorders or fibromyalgia. Animal and human studies have indicated that the activation of peripheral ionotropic glutamate receptors in deep craniofacial tissues may contribute to muscle and temporomandibular joint pain and that sex differences in the activation of glutamate receptors may be involved in the female predominance in temporomandibular disorders and fibromyalgia. A peripheral mechanism involving autocrine and/or paracrine regulation of nociceptive neuronal excitability via injury or inflammation-induced release of glutamate into peripheral tissues that may contribute to the development of craniofacial pain is proposed.

  17. Insufficient pain relief after surgical neuroma treatment : Prognostic factors and central sensitisation

    NARCIS (Netherlands)

    Stokvis, Annemieke; Coert, J. Henk; van Neck, Johan W.

    2010-01-01

    Background: Treatment of patients with neuromatous pain is difficult. Numerous treatment methods have been described, but none has been completely effective in providing sufficient pain relief. Patient-specific prognostic factors, predicting pain after surgical neuroma treatment, can help clinicians

  18. The effect of traditional cupping on pain and mechanical thresholds in patients with chronic nonspecific neck pain : a randomised controlled pilot study

    OpenAIRE

    2012-01-01

    Introduction. Cupping has been used since antiquity in the treatment of pain conditions. In this pilot study, we investigated the effect of traditional cupping therapy on chronic nonspecific neck pain (CNP) and mechanical sensory thresholds. Methods. Fifty CNP patients were randomly assigned to treatment (TG, n = 25) or waiting list control group (WL, n = 25). TG received a single cupping treatment. Pain at rest (PR), pain related to movement (PM), quality of life (SF-36), Neck Disability Ind...

  19. Agmatine reversed mechanical allodynia in a rat model of neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    YANGHong-Ju; ZhAONan; GONGZheng-Hua; YUANWei-Xiou; LIYunFeng; LI-Jin; LUOZhi-Pu

    2004-01-01

    AIM: Agmatine is an endogenous neuromodulator present in the brain and spinal cord, agmatine has both NMDA receptor antagonist and NOS inhibitor activities, which may participate the pathological process in the neuropathic pain. The effect of agmatine on the mechanical allodynia in a rat model of the neuropathic pain was investigated in this experiment.

  20. Role of central arginine vasopressin receptors in the analgesic effect of CDP-choline on acute and neuropathic pain.

    Science.gov (United States)

    Bagdas, Deniz; Yucel-Ozboluk, Hasret; Orhan, Fulya; Kanat, Ozkan; Isbil-Buyukcoskun, Naciye; Gurun, Mine S

    2013-12-04

    Recent studies have demonstrated that arginine vasopressin (AVP) plays a crucial role in pain modulation. In addition, our previous studies have proven that centrally administered cytidine-5'-diphosphate-choline (CDP-choline; citicoline) elicits an analgesic effect in different pain models in rats. Given that CDP-choline enhances central and peripheral vasopressin levels, the present study was designed to investigate the role of central AVP receptors in the analgesic effect of CDP-choline in acute and chronic constriction injury-induced neuropathic pain models. For this purpose, rats were pretreated intracerebroventricularly with the AVP V1 or AVP V2 receptor antagonist 15 min before intracerebroventricular injection of CDP-choline or saline, and pain threshold was determined using the Randall-Selitto test. AVP V1 and AVP V2 receptor antagonist blocked the CDP-choline-induced analgesic effect either in acute or neuropathic models of pain in rats. These results suggest, for the first time, that central AVP receptors are involved in the CDP-choline-elicited analgesic effect.

  1. Mechanisms of nociceptive transduction and transmission: a machinery for pain sensation and tools for selective analgesia.

    Science.gov (United States)

    Binshtok, Alexander M

    2011-01-01

    Many surgical and dental procedures depend on use of local anesthetics to reversibly eliminate pain. By the blockade of voltage-gated sodium channels, local anesthetics prevent the transmission of nociceptive information. However, since all local anesthetics act non-selectively on all types of axons they also cause a loss of innocuous sensation, motor paralysis and autonomic block. Thus, approaches that produce only a selective blockade of pain fibers are of great potential clinical importance. In this chapter we will review the recent findings describing mechanisms of pain transduction and transmission and introduce novel therapeutic approaches to produce pain-selective analgesia.

  2. The influence of negative emotions on pain: behavioral effects and neural mechanisms.

    Science.gov (United States)

    Wiech, Katja; Tracey, Irene

    2009-09-01

    The idea that pain can lead to feelings of frustration, worry, anxiety and depression seems obvious, particularly if it is of a chronic nature. However, there is also evidence for the reverse causal relationship in which negative mood and emotion can lead to pain or exacerbate it. Here, we review findings from studies on the modulation of pain by experimentally induced mood changes and clinical mood disorders. We discuss possible neural mechanisms underlying this modulatory influence focusing on the periaqueductal grey (PAG), amygdala, anterior cingulate cortex (ACC) and anterior insula as key players in both, pain and affective processing.

  3. Neuropathic pain

    Directory of Open Access Journals (Sweden)

    Giuseppe Re

    2009-02-01

    Full Text Available Neuropathic pain is the expression of a dysfunction or primary lesion of a nerve in the peripheral or central nervous system, or both, rather than the biological signal transmitted by the nerve following peripheral nociceptor activation. It represents about 20% of all painful syndromes, with an estimated prevalence of 1.5%, however is actual incidence is hard to pinpoint due to the difficulties encountered in distinguishing it from chronic pain, of which it represents a significant percentage, on account of the not infrequent concurrence of conditions. It is crucial to recognise the variety of symptoms with which it can present: these can be negative and positive and, in turn, motor, sensitive and autonomic. In public health terms, it is important to emphasise that the diagnosis of neuropathic pain does not in most cases require sophisticated procedures and does not therefore weigh on health expenditure. In clinical practice, a validated scale (the LANSS is mentioned is useful for identifying patients presenting neuropathic pain symptoms. Therapy is based on three categories of medication: tricyclic antidepressants, anti-epileptics and opioids at high doses: neuropathic pain has a bad reputation for often resisting common therapeutic approaches and responding less well that nociceptor pain to monotherapy. Therapeutic strategies are all the more adequate the more they are based on symptoms and therefore on the pain generation mechanisms, although the recommendations are dictated more by expert opinions that double-blind randomised trials.

  4. The other mechanism of muscular referred pain: the "connective tissue" theory.

    Science.gov (United States)

    Han, Dong-Gyun

    2009-09-01

    Muscular referred pain, that is, pain perceived in a somatic area other than the site of the noxious stimulation, takes place on a specific place to each muscle in constant and predictable pattern. The central hyperexcitability theory focused on spinal cord, the most proper theory at present, can explain well the segmental pattern of referred pain showing delayed onset. But it is hard to explain the non segmental pattern of referred pain areas of superficial-seated or limb girdle and limb muscles. Referred pain areas of limb girdle and limb muscles appear on the skin above a belt of synergistic muscles beyond the segmental areas. In the case of forearm and calf muscles, referred pain shows up on the palm and sole, the point of force application to the outer object. This finding reflects biomechanical relationship between muscle and its referred pain area. From the phylogenetic perspective, aquatic vertebrated animals (e.g. fish) use myoseptum surrounding myomere, connected to skin to keep tensile strength with it for effective swimming. Likewise, in terrestrial vertebrated animals, there are skin parts weakly interconnected with muscles, though the tensile property of nearly all the skin devolutes except the points of action with the outside. These points are dynamic maximal skin tension areas connected with muscles through superficial fascia, in other words, referred pain areas. Referred pain of deep-seated or truncal muscles appears on the trunk segmentally via spinal cord (the central hyperexcitability theory), but superficial-seated or limb girdle and limb muscles elicit referred pain on dynamic maximal skin tension area through connective tissue (the "connective tissue" theory).

  5. Hyperspectral imaging of endogenous fluorescent metabolic molecules to identify pain states in central nervous system tissue

    Science.gov (United States)

    Staikopoulos, Vasiliki; Gosnell, Martin E.; Anwer, Ayad G.; Mustafa, Sanam; Hutchinson, Mark R.; Goldys, Ewa M.

    2016-12-01

    Fluorescence-based bio-imaging methods have been extensively used to identify molecular changes occurring in biological samples in various pathological adaptations. Auto-fluorescence generated by endogenous fluorescent molecules within these samples can interfere with signal to background noise making positive antibody based fluorescent staining difficult to resolve. Hyperspectral imaging uses spectral and spatial imaging information for target detection and classification, and can be used to resolve changes in endogenous fluorescent molecules such as flavins, bound and free NADH and retinoids that are involved in cell metabolism. Hyperspectral auto-fluorescence imaging of spinal cord slices was used in this study to detect metabolic differences within pain processing regions of non-pain versus sciatic chronic constriction injury (CCI) animals, an established animal model of peripheral neuropathy. By using an endogenous source of contrast, subtle metabolic variations were detected between tissue samples, making it possible to distinguish between animals from non-injured and injured groups. Tissue maps of native fluorophores, flavins, bound and free NADH and retinoids unveiled subtle metabolic signatures and helped uncover significant tissue regions with compromised mitochondrial function. Taken together, our results demonstrate that hyperspectral imaging provides a new non-invasive method to investigate central changes of peripheral neuropathic injury and other neurodegenerative disease models, and paves the way for novel cellular characterisation in health, disease and during treatment, with proper account of intrinsic cellular heterogeneity.

  6. Regional differences of repeatability on visual analogue scale with experimental mechanical pain stimuli.

    Science.gov (United States)

    Hayashi, Kazuhiro; Ikemoto, Tatsunori; Ueno, Takefumi; Arai, Young-Chang P; Shimo, Kazuhiro; Nishihara, Makoto; Suzuki, Shigeyuki; Ushida, Takahiro

    2015-01-12

    Pain-VAS is quite subjective as a scale, but has a tendency to assume differences in repeatability in accordance with perceived pain intensity. The aim of the present study was to investigate the repeatability of regional differences with ratings of pain-VAS. Three experimental mechanical stimuli were applied to twenty seven healthy volunteers across four sessions over four weeks within individuals. The same stimuli were also simultaneously measured in the same manner with an electric balance. The magnitude of mechanical stimuli was determined by 100 g, 300 g, and 600 g monofilaments. Standard deviations (SDs) across measurements with an electric balance showed a regular increase with stimulus magnitude, while coefficient variations (CVs) were constant in each stimulus. On the other hand, although SDs across pain-VAS measurements were significantly greater with the 300 g filament than with the 100 g and 600 g filaments, CVs showed a regular decrease in magnitude of stimulus. These results showed that the CVs of repeated measurement with electric balance were consistent regardless of stimulus intensity, in contrast, CVs of pain-VAS decreased with greater pain rating averaged by repeated measurement. These results suggest that a low rating in pain-VAS is inherently less objective, indicating poor repeatability. In contrast, a high rating in pain-VAS is more objective with better repeatability for experimental pain perception.

  7. EFFECT OF THE CERVICAL ENDURANCE TRAINING PROGRAMME IN MECHANICAL NECK PAIN

    Directory of Open Access Journals (Sweden)

    Pranjal Gogoi

    2015-10-01

    Full Text Available Background: Mechanical neck pain commonly arises insidiously and is generally multifactorial in origin. Regardless of the primary source of pain, the prognosis for individual experiencing chronic neck pain is poor. Exercise interventions are important for effective management of patients with neck pain.the objective of the study is to compare the efficacy of cervical endurance training programme with cervical isometric exercise in alleviating symptoms of mechanical neck pain. Methods: 40 subjects were assessed and identified with Mechanical Neck Pain and recruited for the study and were randomly divided into two groups. In one group endurance training for cervical muscles and in another group resisted isometric had been given for 3 weeks. The post treatment scores regarding endurance, pain intensity, disability, Range of motion and muscle power were compared with the pre treatment scores. Results: Paired‘t’ test was done to compare the pretreatment scores with the post treatment scores .Unpaired ‘t’ test was done to compare the post treatment scores of both the groups. The pain intensity, disability were found to be significantly decreased in experimental group than the control group (p<0.001. While the endurance was found to be significantly increased in experimental group than the control group (p < 0.001. The muscle power was found to be slightly increased in the control group than the experimental group .The post treatment cervical range of motion does not have significant difference in between the groups (Flexion- p=0.35 and Extension-p=0.40. Conclusion: This study showed that the progressive endurance exercise is beneficial in alleviating mechanical neck pain and should be incorporated along with the conventional physiotherapy treatment for mechanical neck pain.

  8. Mechanisms of Sucrose and Non-Nutritive Sucking in Procedural Pain Management in Infants

    Directory of Open Access Journals (Sweden)

    Sharyn Gibbins

    2001-01-01

    Full Text Available The administration of sucrose with and without non-nutritive sucking (NNS has been examined for relieving procedural pain in newborn infants. The calming and pain-relieving effects of sucrose are thought to be mediated by endogenous opioid pathways activated by sweet taste. The orogustatory effects of sucrose have been demonstrated in animal newborns, and in preterm and full term human infants during painful procedures. In contrast to sucrose, the analgesic effects of NNS are hypothesized to be activated through nonopioid pathways by stimulation of orotactile and mechanoreceptor mechanisms. Although there is uncertainty as to whether the effects of sucrose and NNS are synergistic or additive, there is sufficient evidence to support the efficacy of combining the two interventions for procedural pain relief in infants. In this review article, the underlying mechanisms of sucrose and NNS, separately and in combination for relieving procedural pain in preterm and full term infants, are examined. Clinical and research implications are addressed.

  9. Mechanism of neuroadenolysis of the pituitary for cancer pain control

    NARCIS (Netherlands)

    Trouwborst, A.; Yanagida, H.; Erdmann, W.; Kok, A.

    1984-01-01

    Studied whether neuronal activity of the pituitary gland, as related to the primary somatosensory cortex, may be involved in the pain perception pathway influenced by neuroadenolysis of the pituitary. EEG and tooth-pulp EPs (TPEPs) were examined in 3 rhesus monkeys (Macaca mulatta). Findings indicat

  10. McKenzie treatment versus mulligan sustained natural apophyseal glides for chronic mechanical low back pain

    OpenAIRE

    Waqqar, Saira; Shakil-ur-Rehman, Syed; Ahmad, Shakeel

    2016-01-01

    Background and Objective: Chronic mechanical low back pain is common among different age groups and genders. Different manual therapy techniques combined with exercise therapy and electrotherapy modalities play an important role in its management. Our objective was to compare the effects of McKenzie extension exercisesprogram (EEP) versus Mulligan Sustained Natural Apophyseal Glides (SNAGs) for chronic mechanical low back pain (CMLBP). Methods: This randomized control trial (RCT) was conducte...

  11. Exploration of a Novel Persistent Reversal of Pathological Pain: Mechanisms and Mediators

    Science.gov (United States)

    2015-04-01

    cultured glial cells blocked TNF and but not IL-10 production , suggesting that while PKA and PKC may play a role in A2AR agonist effects, there are also...models of neuropathic pain and to elucidate the underlying mechanisms that result in the production of IL-10 and subsequent reversal of the allodynia. 15...translated to numerous animal models of neuropathic pain and to elucidate the underlying mechanisms that result in the production of IL-10 and

  12. Targeting Epigenetic Mechanisms in Pain Due to Trauma and Traumatic Brain Injury (TBI)

    Science.gov (United States)

    2015-10-01

    Pain  ( nociceptive ) sensitization was followed using the von Frey method. Those measures were continued until  the resolution of sensitization. We...AWARD NUMBER: W81XWH-14-1-0579 TITLE: Targeting Epigenetic Mechanisms in Pain due to Trauma and Traumatic Brain Injury (TBI) PRINCIPAL...SUBTITLE Targeting Epigenetic Mechanisms in Pain due to Trauma and Traumatic Brain Injury (TBI) 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0579 5c

  13. Lumbar Mechanics in Tennis Groundstrokes: Differences in Elite Adolescent Players With and Without Low Back Pain.

    Science.gov (United States)

    Campbell, Amity; Straker, Leon; Whiteside, David; O'Sullivan, Peter; Elliott, Bruce; Reid, Machar

    2016-02-01

    Adolescent tennis players are at risk for low back pain (LBP). Recent research has demonstrated a potential mechanical etiology during serves; however, groundstrokes have also been suggested to load this region. Therefore, this study compared lumbar mechanics between players with and without a history of LBP during open and square stance tennis forehands and backhands. Nineteen elite, adolescent, male tennis players participated, 7 with a history of recurrent disabling LBP and 12 without. Differences in three-dimensional lumbar kinetics and kinematics were compared between pain/no pain groups and groundstrokes using linear mixed models (P tennis players.

  14. Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord

    Science.gov (United States)

    Xu, Yang; Liu, Jia; He, Mu; Liu, Ran; Belegu, Visar; Dai, Ping; Liu, Wei; Wang, Wei; Xia, Qing-Jie; Shang, Fei-Fei; Luo, Chao-Zhi; Zhou, Xue; Liu, Su; McDonald, JohnW.; Liu, Jin; Zuo, Yun-Xia; Liu, Fei; Wang, Ting-Hua

    2016-01-01

    Patients with tumors that metastasize to bone frequently suffer from debilitating pain, and effective therapies for treating bone cancer are lacking. This study employed a novel strategy in which herpes simplex virus (HSV) carrying a small interfering RNA (siRNA) targeting platelet-derived growth factor (PDGF) was used to alleviate bone cancer pain. HSV carrying PDGF siRNA was established and intrathecally injected into the cavum subarachnoidale of animals suffering from bone cancer pain and animals in the negative group. Sensory function was assessed by measuring thermal and mechanical hyperalgesia. The mechanism by which PDGF regulates pain was also investigated by comparing the differential expression of pPDGFRα/β and phosphorylated ERK and AKT. Thermal and mechanical hyperalgesia developed in the rats with bone cancer pain, and these effects were accompanied by bone destruction in the tibia. Intrathecal injection of PDGF siRNA and morphine reversed thermal and mechanical hyperalgesia in rats with bone cancer pain. In addition, we observed attenuated astrocyte hypertrophy, down-regulated pPDGFRα/β levels, reduced levels of the neurochemical SP, a reduction in CGRP fibers and changes in pERK/ERK and pAKT/AKT ratios. These results demonstrate that PDGF siRNA can effectively treat pain induced by bone cancer by blocking the AKT-ERK signaling pathway. PMID:27282805

  15. Central hyperexcitability as measured with nociceptive flexor reflex threshold in chronic musculoskeletal pain: a systematic review.

    Science.gov (United States)

    Lim, Edwin Choon Wyn; Sterling, Michele; Stone, Andrew; Vicenzino, Bill

    2011-08-01

    Chronic musculoskeletal conditions are increasingly conceived as involving altered central nervous system processing, and impaired nociceptive flexor reflex (NFR) appears to reflect altered central nervous system processing. The primary objective was to synthesize the evidence for impaired NFR in these conditions. The secondary objective was to evaluate the NFR stimuli parameters employed by reviewed studies. Electronic databases: MEDLINE, CINAHL, Embase, PEDro, Google Scholar, and Cochrane library were searched from the mid-1960s to June 2010. Experimental reports were systematically reviewed and meta-analysis (where possible) was performed. NFR thresholds and parameters of NFR stimuli were extracted. Sixteen trials were identified, 11 of which were suitable for inclusion in the meta-analysis. Compared to healthy controls, standardized mean differences in NFR threshold were significantly lower in subjects with primary headache (-0.45; 95% confidence interval [CI] -0.77 to -0.13, P=0.005), fibromyalgia (-0.63; 95% CI -0.93 to -0.34, Ppain (-1.51; 95% CI -2.10 to -0.93, Pcentral hyperexcitability in people with chronic musculoskeletal pain. Our review also suggests that shorter inter-pulse duration tends to yield smaller variability in NFR threshold. However, further research investigating optimal stimulation parameters is still warranted.

  16. [The pain from burns].

    Science.gov (United States)

    Latarjet, J

    2002-03-01

    The painful events associated with the treatment of a severe burn can, because of their long-lasting and repetitive characteristics, be one of the most excruciating experiences in clinical practice. Moreover, burn pain has been shown to be detrimental to burn patients. Although nociception and peripheral hyperalgesia are considered the major causes of burn pain, the study of more hypothetical mechanisms like central hyperalgesia and neuropathic pain may lead to a better understanding of burn pain symptoms and to new therapeutic approaches. Continuous pain and intermittent pain due to therapeutic procedures are two distinct components of burn pain. They have to be evaluated and managed separately. Although continuous pain is by far less severe than intermittent pain, the treatment is, in both cases, essentially pharmacological relying basically on opioids. Because of wide intra- and inter-individual variations, protocols will have to leave large possibilities of adaptation for each case, systematic pain evaluation being mandatory to achieve the best risk/benefit ratio. Surprisingly, the dose of medication decreases only slowly with time, a burn often remaining painful for long periods after healing. Non pharmacological treatments are often useful and sometimes indispensable adjuncts; but their rationale and their feasibility depends entirely on previous optimal pharmacological control of burn pain. Several recent studies show that burn pain management is inadequate in most burn centres.

  17. Combining opioid and adrenergic mechanisms for chronic pain.

    Science.gov (United States)

    Smith, Howard S; Raffa, Robert B; Pergolizzi, Joseph V; Taylor, Robert; Tallarida, Ronald J

    2014-07-01

    Chronic pain is a highly prevalent medical problem in the United States. Although opioids and serotonin-norepinephrine reuptake inhibitors (SNRIs) have demonstrated efficacy for relief of chronic pain, each has risks of adverse events in patients. Because of the risk of opioid abuse and addiction, combinations reducing opioid requirements are particularly valuable. Opioid and SNRI agents relieve pain by different pathways; concurrent use of each agent separately offers many potential benefits: complementary and possibly synergistic analgesic efficacy, separate titrations of opioid and SNRI effects, and the reduction of opioid requirements. However, few clinical studies have investigated the ideal ratios for combinations of opioids and SNRIs. A number of factors affect whether specific combinations have additive, synergistic, less than additive efficacy, or increase adverse events in patients, including general pharmacokinetic considerations, the potential for pharmacodynamic drug interactions, dose, and timing. Because there is little clinical evidence guiding combination therapy with separate opioid and SNRI agents, using single-molecule agents provides safe and effective therapy and should be the first option presented to patients. The use of empiric combinations of separate opioid and SNRI combinations needs to be considered in light of clinical cautions, including the lack of published evidence to guide dose conversion from any opioid to tramadol or to tapentadol, and vice versa; the need to avoid combinations with known drug interactions; and the need to titrate the dose when adding an SNRI to an opioid, and vice versa.

  18. Mechanisms of disease: mechanism-based classification of neuropathic pain - a critical analysis

    DEFF Research Database (Denmark)

    Finnerup, Nanna Brix; Jensen, Troels Staehelin

    2006-01-01

    Classification of neuropathic pain according to etiology or localization has clear limitations. The discovery of specific molecular and cellular events following experimental nerve injury has raised the possibility of classifying neuropathic pain on the basis of the underlying neurobiological...

  19. Mechanism of inflammatory cytokines in osteoarthritis pain%炎症细胞因子在骨性关节炎疼痛中的作用机制

    Institute of Scientific and Technical Information of China (English)

    姚志华; 裘敏蕾; 樊天佑

    2014-01-01

    In order to provide theoretical basis for the clinical treatment of osteoarthritis, the mechanism of inflammatory cytokines in osteoarthritis pain was investigated. A computer-based search of PubMed and China National Knowledge Infrastructure ( CNKI ) database was performed for the related articles with the keywords of“inflammatory cytokines, interleukin, tumor necrosis factor, chemokines, osteoarthritis pain, neuropathic pain and biochemical mechanisms”in English or in Chinese. The literatures related to the mechanism of inlfammatory cytokines in osteoarthritis pain were selected. A total of 84 literatures were primarily selected and 42 articles were reviewed according to the inclusion criteria. Osteoarthritis pain is one of the main factors affecting the life quality of the patients, and a variety of abnormal cells of the peripheral and central nervous systems were involved. Inlfammatory cytokines played an important role in the pathogenesis of osteoarthritis. The relationship between osteoarthritis pain and common inlfammatory cytokines were reviewed in the review, so as to explore the important role of inlfammatory cytokines in osteoarthritis pain and provide theoretical basis for the clinical treatment of osteoarthritis.

  20. A central analgesic mechanism of acupuncture for migraine An ongoing functional MRI study**

    Institute of Scientific and Technical Information of China (English)

    Lei Lan; Yujie Gao; Fang Zeng; Wei Qin; Mingkai Dong; Mailan Liu; Taipin Guo; Fanrong Liang

    2013-01-01

    Shaoyang acupoints are the most frequently used in migraine treatment. However, the central anal-gesic mechanism remains poorly understood. Studies have demonstrated that single stimulus of the verum acupuncture in healthy subjects can induce significant connectivity or activity changes in pain-related central networks compared with sham acupuncture. However, these findings are not indicative of the central analgesic mechanism of acupuncture at Shaoyang acupoints. Thus, we recruited 100 migraine sufferers and randomly assigned them into five groups: Shaoyang uncommon acupoint, Shaoyang common acupoint, Yangming uncommon acupoint, non-acupoint control, and blank control groups. Subjects were subjected to evaluation of curative effects and functional MRI prior to and after 10 and 20 acupuncture treatments. Al subjects were diagnosed by physicians and enrol ed fol owing clinical physical examination. Subjects were observed during 1-4 weeks after inclusion. At the fifth week, the first clinical evaluation and resting functional MRI were conducted. The Shaoyang uncom-mon acupoint, Shaoyang common acupoint, Yangming uncommon acupoint, and non-acupoint control grousp then were treated with acupuncture, five times per week, 20 times in total over 4 weeks. The second and third clinical evaluations and resting functional MRI screenings were conducted fol owing 10 and 20 acupuncture treatments. The blank control group was observed during the 5 to 8 week pe-riod, fol owed by clinical evaluation and resting functional MRI. The aim of this study was to examine changes in brain functional activity and central networks in subjects with migraine undergoing acu-puncture at Shaoyang uncommon acupoints. This study provides a further explanation of the central analgesic mechanism by which acupuncture at Shaoyang acupoints treats migraine.

  1. Comparison of thermal and mechanical quantitative sensory testing in client-owned dogs with chronic naturally occurring pain and normal dogs.

    Science.gov (United States)

    Freire, Mila; Knazovicky, David; Case, Beth; Thomson, Andrea; Lascelles, B Duncan X

    2016-04-01

    Detecting dogs with central sensitization (CS) secondary to chronic pain is hampered by the current inability to measure this condition. The current study aimed to use quantitative sensory testing (QST) to measure (CS) in normal dogs and dogs with painful degenerative joint disease (DJD). It was hypothesized that QST would differ between these two groups of animals. Mechanical and thermal sensory thresholds obtained in animals with DJD-associated pain on two time points 28 days apart were compared with those of normal dogs. Values of sensory thresholds in DJD dogs obtained 28 days after the first evaluation were significantly lower than the results on the first day of evaluation but no differences were found when these results were compared with those of normal dogs. In conclusion, whether QST is different between dogs with chronic pain and normal dogs needs further investigation using a larger group of animals and age, weight and sex matched groups.

  2. Central action of peripherally applied botulinum toxin type A on pain and dural protein extravasation in rat model of trigeminal neuropathy.

    Directory of Open Access Journals (Sweden)

    Boris Filipović

    Full Text Available BACKGROUND: Infraorbital nerve constriction (IoNC is an experimental model of trigeminal neuropathy. We investigated if IoNC is accompanied by dural extravasation and if botulinum toxin type A (BoNT/A can reduce pain and dural extravasation in this model. METHODOLOGY/PRINCIPAL FINDINGS: Rats which developed mechanical allodynia 14 days after the IoNC were injected with BoNT/A (3.5 U/kg into vibrissal pad. Allodynia was tested by von Frey filaments and dural extravasation was measured as colorimetric absorbance of Evans blue-plasma protein complexes. Presence of dural extravasation was also examined in orofacial formalin-induced pain. Unilateral IoNC, as well as formalin injection, produced bilateral dural extravasation. Single unilateral BoNT/A injection bilaterally reduced IoNC induced dural extravasation, as well as allodynia (lasting more than 2 weeks. Similarly, BoNT/A reduced formalin-induced pain and dural extravasation. Effects of BoNT/A on pain and dural extravasation in IoNC model were dependent on axonal transport through sensory neurons, as evidenced by colchicine injections (5 mM, 2 µl into the trigeminal ganglion completely preventing BoNT/A effects. CONCLUSIONS/SIGNIFICANCE: Two different types of pain, IoNC and formalin, are accompanied by dural extravasation. The lasting effect of a unilateral injection of BoNT/A in experimental animals suggests that BoNT/A might have a long-term beneficial effect in craniofacial pain associated with dural neurogenic inflammation. Bilateral effects of BoNT/A and dependence on retrograde axonal transport suggest a central site of its action.

  3. Neural mechanisms underlying pain's ability to reorient attention: evidence for sensitization of somatic threat detectors.

    Science.gov (United States)

    Dowman, Robert

    2014-06-01

    Pain typically signals damage to the body, and as such can be perceived as threatening and can elicit a strong emotional response. This ecological significance undoubtedly underlies pain's well-known ability to demand attention. However, the neural mechanisms underlying this ability are poorly understood. Previous work from the author's laboratory has reported behavioral evidence suggesting that participants disengage their attention from an incorrectly cued visual target stimulus and reorient it toward a somatic target more rapidly when the somatic target is painful than when it is nonpainful. Furthermore, electrophysiological data suggest that this effect is mediated by a stimulus-driven process, in which somatic threat detectors located in the dorsal posterior insula activate the medial and lateral prefrontal cortex areas involved in reorienting attention toward the painful target. In these previous studies, the painful and nonpainful somatic targets were given in separate experiments involving different participants. Here, the nonpainful and painful somatic targets were presented in random order within the same block of trials. Unlike in the previous studies, both the nonpainful and painful somatic targets activated the somatic threat detectors, and the times taken to disengage and reorient attention were the same for both. These electrophysiological and behavioral data suggest that somatic threat detectors can become sensitized to nonpainful somatic stimuli that are presented in a context that includes painful stimuli.

  4. Psychological flexibility and catastrophizing as associated change mechanisms during online Acceptance & Commitment Therapy for chronic pain.

    Science.gov (United States)

    Trompetter, Hester R; Bohlmeijer, Ernst T; Fox, Jean-Paul; Schreurs, Karlein M G

    2015-11-01

    The underlying mechanisms of the effectiveness of cognitive behavioural interventions for chronic pain need further clarification. The role of, and associations between, pain-related psychological flexibility (PF) and pain catastrophizing (PC) were examined during a randomized controlled trial on internet-based Acceptance & Commitment Therapy (ACT) for chronic pain. We assessed (1) the unique and combined indirect effects of PF and PC on outcomes, and (2) the causality of relations between PF, PC and the primary outcome pain interference in daily life (MPI) during ACT. A total of 238 pain sufferers were allocated to either ACT, a control condition on Expressive Writing, or a waiting list condition. Non-parametric cross-product of coefficients mediational analyses and cross-lagged panel designs were applied. Compared to control conditions, both baseline to post-intervention changes in PF and PC seemed to uniquely mediate baseline to three-month follow-up changes in pain interference and psychological distress. Only PF mediated changes in pain intensity. Indirect effects were twice as large for PF (κ2 = .09-.19) than for PC (κ² PCS = .05-.10). Further assessment of changes during ACT showed, however, that only PF, and not PC, predicted subsequent changes in MPI, while early and late changes in both PF and PC predicted later changes in each other. In conclusion, only PF functioned as a direct, causal working mechanism during ACT, with larger indirect effects that occurred earlier than changes in PC. Additionally, PC may function as an indirect mechanism of change during ACT for chronic pain via its direct influence on PF.

  5. Vagus nerve stimulation for epilepsy: A review of central mechanisms

    OpenAIRE

    Krahl, Scott E.; Clark, Kevin B.

    2012-01-01

    In a previous paper, the anatomy and physiology of the vagus nerve was discussed in an attempt to explain which vagus nerve fibers and branches are affected by clinically relevant electrical stimulation. This companion paper presents some of vagus nerve stimulation's putative central nervous system mechanisms of action by summarizing known anatomical projections of vagal afferents and their effects on brain biogenic amine pathways and seizure expression.

  6. Managing phantom pain.

    Science.gov (United States)

    Manchikanti, Laxmaiah; Singh, Vijay

    2004-07-01

    Since the first medical description of post-amputation phenomena reported by Ambrose Paré, persistent phantom pain syndromes have been well recognized. However, they continue to be difficult to manage. The three most commonly utilized terms include phantom sensation, phantom pain, and stump pain. Phantom limb sensation is an almost universal occurrence at some time during the first month following surgery. However, most phantom sensations generally resolve after two to three years without treatment, except in the cases where phantom pain develops. The incidence of phantom limb pain has been reported to vary from 0% to 88%. The incidence of phantom limb pain increases with more proximal amputations. Even though phantom pain may diminish with time and eventually fade away, it has been shown that even two years after amputation, the incidence is almost the same as at onset. Consequently, almost 60% of patients continue to have phantom limb pain after one year. In addition, phantom limb pain may also be associated with multiple pain problems in other areas of the body. The third symptom, stump pain, is located in the stump itself. The etiology and pathophysiological mechanisms of phantom pain are not clearly defined. However, both peripheral and central neural mechanisms have been described, along with superimposed psychological mechanisms. Literature describing the management of phantom limb pain or stump pain is in its infancy. While numerous treatments have been described, there is little clinical evidence supporting drug therapy, psychological therapy, interventional techniques or surgery. This review will describe epidemiology, etiology and pathophysiological mechanisms, risk factors, and treatment modalities. The review also examines the effectiveness of various described modalities for prevention, as well as management of established phantom pain syndromes.

  7. Hip fracture presenting as mechanical low back pain subsequent to a fall: a case study

    OpenAIRE

    Gleberzon, Brian; Hyde, David

    2006-01-01

    This case chronicles the assessment and clinical management of a 54 year old female patient who presented with post traumatic lower back, hip and lower extremity pain, initially attributed to mechanical low back pain but ultimately diagnosed as a hip fracture. This case study illustrates a number of important issues germane to chiropractic care. These are; the importance of using different assessment procedures, combined with clinical experience, in order to differentiate between those patien...

  8. Efficacy of methylprednisolone versus other pharmacologic interventions for the treatment of central post-stroke pain: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Pellicane AJ

    2013-07-01

    Full Text Available Anthony J Pellicane, Scott R Millis Department of Physical Medicine and Rehabilitation, Wayne State University School of Medicine, Rehabilitation Institute of Michigan in the Detroit Medical Center, Detroit, MI, USA Purpose: To determine if an oral, tapered methylprednisolone regimen is superior to other commonly used pharmacologic interventions for the treatment of central post-stroke pain (CPSP. Patients and methods: In this study, the charts of 146 stroke patients admitted to acute inpatient rehabilitation were retrospectively reviewed. Patients diagnosed with CPSP underwent further chart review to assess numerical rating scale for pain scores and as-needed pain medication usage at different time points comparing CPSP patients treated with methylprednisolone to those treated with other pharmacologic interventions. Results: In the sample, 8.2% were diagnosed with CPSP during acute care or inpatient rehabilitation. Mean numerical rating scale for pain scores day of symptom onset did not differ between those patients treated with methylprednisolone versus those treated with other pharmacologic interventions (mean ± standard deviation; 6.1 ± 2.3 versus 5.7 ± 1.6, P = 0.77. However, mean numerical rating scale for pain scores differed significantly 1-day after treatment initiation (1.7 ± 2.1 versus 5.0 ± 1.9, P = 0.03 and 1-day prior to rehabilitation discharge (0.3 ± 0.9 versus 4.1 ± 3.2, P = 0.01 between the two groups. Compared to day of symptom onset, as-needed pain medication usage within the methylprednisolone group was marginally less 1-day after treatment initiation (Z = -1.73, P = 0.08 and 1-day prior to rehabilitation discharge (Z = -1.89, P = 0.06. No difference in as-needed pain medication usage existed within the non-steroid group at the same time points. Conclusion: Methylprednisolone is a potential therapeutic option for CPSP. The findings herein warrant study in prospective trials. Keywords: stroke, pain, central post

  9. SHORT TERM EFFICACY OF KINESIOTAPING AND EXERCISES ON CHRONIC MECHANICAL NECK PAIN

    Directory of Open Access Journals (Sweden)

    Kulkarni Prachi Sanjay 1 , 2 , 3 ,

    2013-12-01

    Full Text Available Background and introduction:The purpose of study is to determine the short term effectiveness of Kinesiotapingcombined with Exercises in reducing pain and improving Cervical range of motion and functional ability forsubjects with Chronic Mechanical Neck pain.Method::Pre to post test experimental study design randomised thirty Chronic Mechanical Neck pain patientseach 15 into KT and control group. KT group received kinesiotaping with exercises and Control groupreceivedonly exercises for 3 times a week for 4 weeks.Pain, active cervical range of motion and functional ability weremeasured before and after 4 weeks of intervention.Results:Comparative analysis using Independent‘t’ test and Mann Whitney U test found that there is a statisticallysignificant difference (p<0.05 in means of NPRS, active Flexion, Extension, Rotation to right, Rotation to LeftROM, Neck Disability Index (NDI in percentage when compared post intervention means between the groups.Pre to post test within the group analysis in both the groups using Paired‘t’ test and Wilcoxon signed rank testfound that there is a statistically significant change in means of NPRS, Flexion, Extension, Rotation to right,Rotation to Left ROM, NDI.Conclusion:Kinesiotaping combined with exercises for 4 weeks found short term effect in improving pain,active cervical ROM and functional ability than exercises alone in treatment of chronic Mechanical neck pain

  10. Role of COX-1 in the process of neuropathic pain and its mechanism Zhi-hong LU, Qi - bing MEI

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    AIM In neuropathic pain the peripheral or central nervous systems are malfunctioning and become the cause of the pain. Unlike other pain styles, most neuropathic pain responds poorly to opioid analgesics. The mainstay of treatment is predominantly the tricyclic antidepressants, the anticonvulsants and the systemic local anesthetics of which the long- term use could lead to great side effects. Recently, proin-flammatory cytokines, such as IL-6, TNF-α, etc, have been proved to be involved in the process of neuropathic pain, indicating the cross - talking between neuropathic pain and inflammation. As an important member in inflammatory process, COX is expected to play a part in the process of neuropathic pain.In this study, we observed the change of COX-1 after neuropathic pain and further investigated thechange it caused in the brain. METHODS Spared nerve injury (SNI) is used to induce neuropathic painin mice.

  11. The role of TRPA1 in muscle pain and mechanical hypersensitivity under inflammatory conditions in rats.

    Science.gov (United States)

    Asgar, J; Zhang, Y; Saloman, J L; Wang, S; Chung, M-K; Ro, J Y

    2015-12-03

    Transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is expressed in muscle afferents and direct activation of these receptors induces acute mechanical hypersensitivity. However, the functional role of TRPA1 under pathological muscle pain conditions and mechanisms by which TRPA1 mediate muscle pain and hyperalgesia are not clearly understood. Two rodent behavioral models validated to assess craniofacial muscle pain conditions were used to study ATP- and N-Methyl-D-aspartate (NMDA)-induced acute mechanical hypersensitivity and complete Freund's adjuvant (CFA)-induced persistent mechanical hypersensitivity. The rat grimace scale (RGS) was utilized to assess inflammation-induced spontaneous muscle pain. Behavioral pharmacology experiments were performed to assess the effects of AP18, a selective TRPA1 antagonist under these conditions. TRPA1 expression levels in trigeminal ganglia (TG) were examined before and after CFA treatment in the rat masseter muscle. Pre-treatment of the muscle with AP18 dose-dependently blocked the development of acute mechanical hypersensitivity induced by NMDA and α,β-methylene adenosine triphosphate (αβmeATP), a specific agonist for NMDA and P2X3 receptor, respectively. CFA-induced mechanical hypersensitivity and spontaneous muscle pain responses were significantly reversed by post-treatment of the muscle with AP18 when CFA effects were most prominent. CFA-induced myositis was accompanied by significant up-regulation of TRPA1 expression in TG. Our findings showed that TRPA1 in muscle afferents plays an important role in the development of acute mechanical hypersensitivity and in the maintenance of persistent muscle pain and hypersensitivity. Our data suggested that TRPA1 may serve as a downstream target of pro-nociceptive ion channels, such as P2X3 and NMDA receptors in masseter afferents, and that increased TRPA1 expression under inflammatory conditions may contribute to the maintenance of persistent muscle pain

  12. Pathogenesis of Painful Diabetic Neuropathy

    Directory of Open Access Journals (Sweden)

    Amir Aslam

    2014-01-01

    Full Text Available The prevalence of diabetes is rising globally and, as a result, its associated complications are also rising. Painful diabetic neuropathy (PDN is a well-known complication of diabetes and the most common cause of all neuropathic pain. About one-third of all diabetes patients suffer from PDN. It has a huge effect on a person’s daily life, both physically and mentally. Despite huge advances in diabetes and neurology, the exact mechanism of pain causation in PDN is still not clear. The origin of pain could be in the peripheral nerves of the central nervous system. In this review, we discuss various possible mechanisms of the pathogenesis of pain in PDN. We discuss the role of hyperglycaemia in altering the physiology of peripheral nerves. We also describe central mechanisms of pain.

  13. The effectiveness of Long's manipulation on patients with chronic mechanical neck pain: a randomized controlled trial.

    Science.gov (United States)

    Lin, Jian Hua; Shen, Tong; Chung, Raymond Chi Keung; Chiu, Thomas Tai Wing

    2013-08-01

    Long's manipulation (LM) is a representative Chinese manipulation approach incorporating both spinal manipulation and traditional Chinese massage (TCM) techniques. This randomized controlled trial (RCT) aimed to compare the immediate and short-term relative effectiveness of LM to TCM on patients with chronic neck pain. Patients were randomly assigned to either LM group or TCM group. LM group was treated with Long's manipulation, while the TCM group received TCM therapy. Patients attended 8 sessions of treatment (one session every three days). Outcome measures included neck disability (Northwick Park Neck Pain Questionnaire; NPQ), pain intensity (Numeric Pain Rating Scale; NPRS), patient perceived satisfaction of care (PPS) (11-point scale), craniovertebral angle (CV angle) and cervical range of motion (ROM). A blinded assessor performed assessment at baseline, immediate after treatment and 3 months post treatment. LM group achieved significantly greater improvement than TCM group in pain intensity (p angle and most of cervical ROM between groups (p = 0.169 ∼ 0.888) with an exception of flexion at 3-month follow-up (p = 0.005). This study shows that LM could produce better effects than TCM in relieving pain and improving disability in the management of patients with chronic mechanical neck pain.

  14. The immediate effects of cervical spine manipulative therapy and mobilization on local skin temperature, in mechanical neck pain

    OpenAIRE

    2012-01-01

    M.Tech. Purpose: Mechanical neck pain is the most common type of cervical spine pain encountered. It is also referred to as simple or non-specific neck pain, and is common in all groups of people. Often the exact cause of the pain is unknown. Neck pain, although felt in the neck, can be caused by numerous spinal problems. Neck pain may arise due to muscular tightness in both the neck and upper back, or due to entrapment of nerves of the cervical vertebrae. Joint dysfunction in the cervical...

  15. Peripheral and spinal mechanisms of nociception in a rat reserpine-induced pain model.

    Science.gov (United States)

    Taguchi, Toru; Katanosaka, Kimiaki; Yasui, Masaya; Hayashi, Koei; Yamashita, Mai; Wakatsuki, Koji; Kiyama, Hiroshi; Yamanaka, Akihiro; Mizumura, Kazue

    2015-03-01

    Chronic widespread pain is a serious medical problem, yet the mechanisms of nociception and pain are poorly understood. Using a reserpine-induced pain model originally reported as a putative animal model for fibromyalgia, this study was undertaken to examine the following: (1) expression of several ion channels responsible for pain, mechanotransduction, and generation/propagation of action potentials in the dorsal root ganglion (DRG), (2) activities of peripheral nociceptive afferents, and (3) alterations in spinal microglial cells. A significant increase in mRNA expression of the acid-sensing ion channel (ASIC)-3 was detected in the DRG, and the behavioral mechanical hyperalgesia was significantly reversed by subcutaneous injection of APETx2, a selective blocker of ASIC3. Single-fiber recordings in vitro revealed facilitated mechanical responses of mechanoresponsive C-fibers both in the skin and muscle although the proportion of mechanoresponsive C-nociceptors was paradoxically decreased. In the spinal dorsal horn, microglial cells labeled with Iba1 immunoreactivity was activated, especially in laminae I-II where the nociceptive input is mainly processed compared with the other laminae. The activated microglia and behavioral hyperalgesia were significantly tranquilized by intraperitoneal injection of minocycline. These results suggest that the increase in ASIC3 in the DRG facilitated mechanical response of the remaining C-nociceptors and that activated spinal microglia may direct to intensify pain in this model. Pain may be further amplified by reserpine-induced dysfunction of the descending pain inhibitory system and by the decrease in peripheral drive to this system resulting from a reduced proportion of mechanoresponsive C-nociceptors.

  16. Assessment of Effectiveness of Percutaneous Adhesiolysis in Managing Chronic Low Back Pain Secondary to Lumbar Central Spinal Canal Stenosis

    Directory of Open Access Journals (Sweden)

    Laxmaiah Manchikanti, Kimberly A. Cash, Carla D. McManus, Vidyasagar Pampati

    2013-01-01

    Full Text Available Background: Chronic persistent low back and lower extremity pain secondary to central spinal stenosis is common and disabling. Lumbar surgical interventions with decompression or fusion are most commonly performed to manage severe spinal stenosis. However, epidural injections are also frequently performed in managing central spinal stenosis. After failure of epidural steroid injections, the next sequential step is percutaneous adhesiolysis and hypertonic saline neurolysis with a targeted delivery. The literature on the effectiveness of percutaneous adhesiolysis in managing central spinal stenosis after failure of epidural injections has not been widely studied.Study Design: A prospective evaluation.Setting: An interventional pain management practice, a specialty referral center, a private practice setting in the United States.Objective: To evaluate the effectiveness of percutaneous epidural adhesiolysis in patients with chronic low back and lower extremity pain with lumbar central spinal stenosis.Methods: Seventy patients were recruited. The initial phase of the study was randomized, double-blind with a comparison of percutaneous adhesiolysis with caudal epidural injections. The 25 patients from the adhesiolysis group continued with follow-up, along with 45 additional patients, leading to a total of 70 patients. All patients received percutaneous adhesiolysis and appropriate placement of the Racz catheter, followed by an injection of 5 mL of 2% preservative-free lidocaine with subsequent monitoring in the recovery room. In the recovery room, each patient also received 6 mL of 10% hypertonic sodium chloride solution, and 6 mg of non-particulate betamethasone, followed by an injection of 1 mL of sodium chloride solution and removal of the catheter.Outcomes Assessment: Multiple outcome measures were utilized including the Numeric Rating Scale (NRS, the Oswestry Disability Index 2.0 (ODI, employment status, and opioid intake with assessment at 3, 6

  17. Multimodal pain stimulation of the gastrointestinal tract

    Institute of Scientific and Technical Information of China (English)

    Asbjφrn Mohr Drewes; Hans Gregersen

    2006-01-01

    Understanding and characterization of pain and other sensory symptoms are among the most important issues in the diagnosis and assessment of patient with gastrointestinal disorders. Methods to evoke and assess experimental pain have recently developed into a new area with the possibility for multimodal stimulation (e.g.,electrical, mechanical, thermal and chemical stimulation)of different nerves and pain pathways in the human gut. Such methods mimic to a high degree the pain experienced in the clinic. Multimodal pain methods have increased our basic understanding of different peripheral receptors in the gut in health and disease. Together with advanced muscle analysis, the methods have increased our understanding of receptors sensitive to mechanical,chemical and temperature stimuli in diseases, such as systemic sclerosis and diabetes. The methods can also be used to unravel central pain mechanisms, such as those involved in allodynia, hyperalgesia and referred pain. Abnormalities in central pain mechanisms are often seen in patients with chronic gut pain and hence methods relying on multimodal pain stimulation may help to understand the symptoms in these patients.Sex differences have been observed in several diseases of the gut, and differences in central pain processing between males and females have been hypothesized using multimodal pain stimulations. Finally, multimodal methods have recently been used to gain more insight into the effect of drugs against pain in the GI tract.Hence, the multimodal methods undoubtedly represents a major step forward in the future characterization and treatment of patients with various diseases of the gut.

  18. Effect of TENS on pain in relation to central sensitization in patients with osteoarthritis of the knee: study protocol of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Beckwée David

    2012-02-01

    Full Text Available Abstract Background Central sensitization has recently been documented in patients with knee osteoarthritis (OAk. So far, the presence of central sensitization has not been considered as a confounding factor in studies assessing the pain inhibitory effect of tens on osteoarthritis of the knee. The purpose of this study is to explore the pain inhibitory effect of burst tens in OAk patients and to explore the prognostic value of central sensitization on the pain inhibitory effect of tens in OAk patients. Methods Patients with knee pain due to OAk will be recruited through advertisements in local media. Temporal summation, before and after a heterotopic noxious conditioning stimulation, will be measured. In addition, pain on a numeric rating score, WOMAC subscores for pain and function and global perceived effect will be assessed. Patients will be randomly allocated to one of two treatment groups (tens, sham tens. Follow-up measurements will be scheduled after a period of 6 and 12 weeks. Discussion Tens influences pain through the electrical stimulation of low-threshold A-beta cutaneous fibers. The responsiveness of central pain-signaling neurons of centrally sensitized OAk patients may be augmented to the input of these electrical stimuli. This would encompass an adverse therapy effect of tens. To increase treatment effectiveness it might be interesting to identify a subgroup of symptomatic OAk patients, i.e., non-sensitized patients, who are likely to benefit from burst tens. Trial Registration ClinicalTrials.gov: NCT01390285

  19. Dor: aspectos atuais da sensibilização periférica e central Dolor: aspectos actuales de la sensibilización periférica y central Pain: current aspects on peripheral and central sensitization

    Directory of Open Access Journals (Sweden)

    Anita Perpétua Carvalho Rocha

    2007-02-01

    conducción nerviosa central y periférica.BACKGROUND AND OBJECTIVES: Current research has focused on the biochemical and structural plasticity of the nervous system secondary to tissue injury. The mechanisms involved in the transition from acute to chronic pain are complex and involve the interaction of receptor systems and the flow of intracellular ions, second messenger systems, and new synaptic connections. The aim of this article was to discuss the new mechanisms concerning peripheral and central sensitization. CONTENTS: Tissue injury increases the response of nociceptors, known as sensitization or facilitation. These phenomena begin after the local release of inflammatory mediators and the activation of the cells of the immune system or specific receptors in the peripheral and central nervous system. CONCLUSIONS: Tissue and neuronal lesions result in sensitization of the nociceptors and facilitation of the central and peripheral nervous conduction.

  20. Entropy as a new measure of mechanical pain sensitivity in the masseter muscle

    DEFF Research Database (Denmark)

    Castrillon, Eduardo; Sato, Hitoshi; Tanosoto, Tomohiro

    ENTROPY AS A NEW MEASURE OF MECHANICAL PAIN SENSITIVITY IN THE MASSETER MUSCLE Author Block: E. E. Castrillon1, H. Sato2,3, T. Tanosoto4, T. Arima4, L. Baad-Hansen1, P. Svensson1, 1Clinical Oral Physiology, Århus Univ., Aarhus, Denmark, 2Dept. of Dentistry & Oral Physiology, Sch. of Med., Keio Un...... injections (Pmechanical pain sensitivity that captures new aspects of spatial characteristics and could therefore complement more classical assessments of TMD pain patients.......ENTROPY AS A NEW MEASURE OF MECHANICAL PAIN SENSITIVITY IN THE MASSETER MUSCLE Author Block: E. E. Castrillon1, H. Sato2,3, T. Tanosoto4, T. Arima4, L. Baad-Hansen1, P. Svensson1, 1Clinical Oral Physiology, Århus Univ., Aarhus, Denmark, 2Dept. of Dentistry & Oral Physiology, Sch. of Med., Keio Univ......., Tokyo, Japan, 3Japan Society for the Promotion of Sci., Tokyo, Japan, 4Dept. of Oral Rehabilitation, Graduate Sch. of Dental Med., Hokkaido Univ., Sapporo, Japan : Aim of Investigation: Manual palpation is a psychophysical technique to evaluate mechanical pain sensitivity in craniofacial muscles...

  1. Mechanisms of nerve capping technique in prevention of painful neuroma formation.

    Directory of Open Access Journals (Sweden)

    Hede Yan

    Full Text Available Nerve capping techniques have been introduced as a promising treatment modality for the treatment of painful neuroma with varied outcomes; however, its exact mechanism is still unknown. RhoA is one of the members of the RAS superfamily of GTPases that operate as molecular switches and plays an important role in peripheral nerve regeneration. Our aim was to investigate the structural and morphologic mechanisms by which the nerve capping technique prevents the formation of painful neuromas after neuroectomy. We also hoped to provide a theoretical basis for this treatment approach. An aligned nanofiber conduit was used for the capping procedure and the sciatic nerve of Sprague-Dawley rats was selected as the animal model. Behavioral analysis, extent of neuroma formation, histological assessment, expressions of pain markers of substance P and c-fos, molecular biological changes as well as ultrastructural features were investigated and compared with the findings in a no-capping control group. The formation of traumatic neuromas was significantly inhibited in the capping group with relatively "normal" structural and morphological features and no occurrence of autotomy and significantly lower expression of pain markers compared to the no-capping group. The gene expression of RhoA was consistently in a higher level in the capping group within 8 weeks after surgery. This study shows that capping technique will alter the regeneration state of transected nerves and reduce painful neuroma formation, indicating a promising approach for the treatment of painful neuroma. The initiation of the "regenerative brake" induced by structural as well as morphological improvements in the severed nerve is theorized to be most likely a key mechanism for the capping technique in the prevention of painful neuroma formation.

  2. The stress response to surgery: release mechanisms and the modifying effect of pain relief

    DEFF Research Database (Denmark)

    Kehlet, H

    1989-01-01

    This short review updates information on the release mechanisms of the systemic response to surgical injury and the modifying effect of pain relief. Initiation of the response is primarily due to afferent nerve impulses combined with release of humoral substances (such as prostaglandins, kinins...... in releasing the classical endocrine catabolic response, while humoral factors are important for the hyperthermic response, changes in coagulation and fibrinolysis immunofunction, and capillary permeability. The modifying effect of pain relief on the surgical stress response is dependent upon the technique...... on the stress response. In summary, pain alleviation itself may not necessarily lead to an important modification of the stress response, and a combined approach with inhibition of the neural and humoral release mechanisms is necessary for a pronounced inhibition or prevention of the response to surgical injury....

  3. Pain in Down's Syndrome

    Directory of Open Access Journals (Sweden)

    Federica Mafrica

    2006-01-01

    Full Text Available Pain is a homeostatic mechanism that intervenes to protect the organism from harmful stimuli that could damage its integrity. It is made up of two components: the sensory-discriminative component, which identifies the provenance and characteristics of the type of pain; and the affective-motivational component, on which emotional reflexes, following the painful sensation, depend.There is a system for pain control at an encephalic and spinal level, principally made up of the periaqueductal grey matter, the periventricular area, the nucleus raphe magnus, and the pain-inhibition complex situated in the posterior horns of the spinal cord. Through the activation of these pain-control systems, the nervous system suppresses the afference of pain signals. Endogenous opioids represent another analgesic system.In the course of various studies on pain transmission in Down patients, the reduced tolerance of pain and the incapacity to give a qualitative and quantitative description emerged in a powerful way. All of these aspects cause difficulty in evaluating pain. This is linked to several learning difficulties. However, it cannot be excluded that in these anomalies of pain perception, both the anatomical and the neurotransmitter alteration, typical of this syndrome, may hold a certain importance.This fact may have important clinical repercussions that could affect the choice of therapeutic and rehabilitative schemes for treatment of pathologies in which pain is the dominant symptom, such as postoperative pain. It could influence research on analgesics that are more suitable for these patients, the evaluation of the depth of analgesia during surgical operation, and ultimately, absence of obvious pain manifestations. In conclusion, alterations of the central nervous system, neurotransmitters, pain transmission, and all related problems should be considered in the management of pain in patients with Down's syndrome, especially by algologists and

  4. Central chemoreceptors and neural mechanisms of cardiorespiratory control

    Directory of Open Access Journals (Sweden)

    T.S. Moreira

    2011-09-01

    Full Text Available The arterial partial pressure (P CO2 of carbon dioxide is virtually constant because of the close match between the metabolic production of this gas and its excretion via breathing. Blood gas homeostasis does not rely solely on changes in lung ventilation, but also to a considerable extent on circulatory adjustments that regulate the transport of CO2 from its sites of production to the lungs. The neural mechanisms that coordinate circulatory and ventilatory changes to achieve blood gas homeostasis are the subject of this review. Emphasis will be placed on the control of sympathetic outflow by central chemoreceptors. High levels of CO2 exert an excitatory effect on sympathetic outflow that is mediated by specialized chemoreceptors such as the neurons located in the retrotrapezoid region. In addition, high CO2 causes an aversive awareness in conscious animals, activating wake-promoting pathways such as the noradrenergic neurons. These neuronal groups, which may also be directly activated by brain acidification, have projections that contribute to the CO2-induced rise in breathing and sympathetic outflow. However, since the level of activity of the retrotrapezoid nucleus is regulated by converging inputs from wake-promoting systems, behavior-specific inputs from higher centers and by chemical drive, the main focus of the present manuscript is to review the contribution of central chemoreceptors to the control of autonomic and respiratory mechanisms.

  5. The effectiveness of thoracic manipulation on patients with chronic mechanical neck pain - a randomized controlled trial.

    Science.gov (United States)

    Lau, Herman Mun Cheung; Wing Chiu, Thomas Tai; Lam, Tai-Hing

    2011-04-01

    The aim of our study was to assess the effectiveness of thoracic manipulation (TM) on patients with chronic neck pain. 120 patients aged between 18 and 55 were randomly allocated into two groups: an experimental group which received TM and a control group without the manipulative procedure. Both groups received infrared radiation therapy (IRR) and a standard set of educational material. TM and IRR were given twice weekly for 8 sessions. Outcome measures included craniovertebral angle (CV angle), neck pain (Numeric Pain Rating Scale; NPRS), neck disability (Northwick Park Neck Disability Questionnaire; NPQ), health-related quality of life status (SF36 Questionnaire) and neck mobility. These outcome measures were assessed immediately after 8 sessions of treatment, 3-months and at a 6-month follow-up. Patients that received TM showed significantly greater improvement in pain intensity (p = 0.043), CV angle (p = 0.049), NPQ (p = 0.018), neck flexion (p = 0.005), and the Physical Component Score (PCS) of the SF36 Questionnaire (p = 0.002) than the control group immediately post-intervention. All these improvements were maintained at the 6-month follow-ups. This study shows that TM was effective in reducing neck pain, improving dysfunction and neck posture and neck range of motion (ROM) for patients with chronic mechanical neck pain up to a half-year post-treatment.

  6. 疼痛共情的神经机制%Neural Mechanisms Underlying Empathy for Pain

    Institute of Scientific and Technical Information of China (English)

    程真波; 黄宇霞

    2012-01-01

    one's and others' pain in the ACC and AI and then used them as seed regions for two kinds of functional connectivity analyses. Their analyses identified clusters in the midbrain and periaqueductal gray with greater connectivity to the AI during one's own pain as opposed to other pain. The opposite pattern was found in the dorsal medial prefrontal cortex that showed greater connectivity to the ACC and AI during other pain than during self pain. This demonstrated that regions showing similar activity during one's and other's pain may nonetheless be part of distinct functional networks ; these networks could not have been detected in prior work that examined overlaps between one's and other's pain in terms of average activity, but not connectivity. Empathy, however, is a complex construct consisting not only of emotional but also of cognitive and somatomotor components. The sensory dimension of pain is mainly coded in parietal sensorimotor neural structures, including the somatosensory cortices. Thus, it is entirely possible that empathy may also rely on basic resonant mechanisms that allow mapping others' sensation onto one' s own sensorimotor system. Single-pulse TM5 may provide indirect information about the sensorimotor structures involved in this mapping. The primary somatosensory cortex (S1) is involved in pain and touch shared representations by recording somatosensory-evoked potentials during the direct observation of painful and nonpainful stimuli delivered to a human model' s hand. This paper reviews the research advance in the field of the neural bases of empathy for pain from the perspective of the affective aspect and the sensory aspect respectively. Future studies should pay more attention to the research technologies, analysis methods and experimental manipulation.%疼痛是一种多维度的体验。情感成分和感觉成分是疼痛体验的主要成分,二者有着不同的神经机制。疼痛共情是痛觉“共鸣”的

  7. Psychosocial mechanisms of the pain and quality of life relationship for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)

    Science.gov (United States)

    Krsmanovic, Adrijana; Tripp, Dean A.; Nickel, J. Curtis; Shoskes, Daniel A.; Pontari, Michel; Litwin, Mark S.; McNaughton-Collins, Mary F.

    2014-01-01

    Introduction: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent, chronic pelvic pain condition largely unresponsive to medical interventions. Psychosocial risk factors are associated with poor outcomes in CP/CPPS, but have not been examined for their intervening roles between pain and reduced quality of life (QoL). This study aimed to determine if psychosocial risk factors (i.e., patient coping and catastrophizing) mediate the association between pain and QoL. Methods: Using a cross sectional design, 175 men with CP/CPPS (mean age 46.83; SD 10.86) were recruited from tertiary care urology clinics and completed questionnaires on demographics, pain, QoL, pain coping, depression, and catastrophizing. An exploratory factor analysis was conducted and aggregate factor scores were examined to improve the amount of meaningful measurement to be used in multiple mediations. The models specified multiple risk factors as mechanisms between pain and both physical and mental QoL as the primary outcome measurements. Results: Four aggregate psychosocial factor scores were produced from the psychosocial measures (i.e., illness and wellness-focused behavioural coping, depression and catastrophizing). Illness-focused coping partially mediated the relationship between pain and physical QoL. However, catastrophizing and illness-focused coping fully mediated the relation between pain and mental QoL, showing the association between pain and mental QoL was no longer significant when catastrophizing and illness-focused coping were in the model. Conclusion: Psychosocial factors function as mechanisms between higher pain and they are associated diminished mental QoL. These results introduce illness-focused coping as an important biopsychosocial target in CP/CPPS management. PMID:25553153

  8. Topical lidocaine patch 5% may target a novel underlying pain mechanism in osteoarthritis.

    Science.gov (United States)

    Galer, Bradley S; Sheldon, Eric; Patel, Nileshkumar; Codding, Chris; Burch, Francis; Gammaitoni, Arnold R

    2004-09-01

    Recent literature and animal research has provided insight to potentially new analgesic targets for managing osteoarthritis (OA) pain. Primary afferent neurons located in affected joints express excessive amounts of abnormally functioning sodium (Na) channels on their surface in response to the inflammatory process. These Na channels may play an integral role in production of pain and hyperalgesia. Hence, the authors set out to conduct a 2-week, open-label, multicenter proof-of-concept study to evaluate the effectiveness and safety of lidocaine patch 5% monotherapy in adults with OA pain of the knee (n = 20). Patients with OA of one or both knees who were experiencing inadequate pain relief (defined as an average daily pain intensity of > 4 on a 0 to 10 pain scale) with their current analgesic regimen (i.e. APAP, NSAIDs, COX-2 inhibitors, tramadol) were enrolled and had all analgesic medications discontinued. Treatment with the lidocaine patch 5% resulted in significant improvements in the Western Ontario and McMaster Universities OA Index (WOMAC) pain, stiffness, physical function subscales and composite index (48.4, 41.1, 47.0, and 46.8% improvements respectively, p lidocaine patch 5% was generally well tolerated and no patients discontinued due to treatment-related adverse events. Given the open-label design, lack of a control group, and small sample size, the findings from our pilot study need to be confirmed by larger randomized controlled trials. Topical lidocaine patch 5% may provide clinicians with a novel, non-systemic therapy for OA pain with a unique mechanism of action.

  9. The effect of traditional cupping on pain and mechanical thresholds in patients with chronic nonspecific neck pain: a randomised controlled pilot study.

    Science.gov (United States)

    Lauche, Romy; Cramer, Holger; Hohmann, Claudia; Choi, Kyung-Eun; Rampp, Thomas; Saha, Felix Joyonto; Musial, Frauke; Langhorst, Jost; Dobos, Gustav

    2012-01-01

    Introduction. Cupping has been used since antiquity in the treatment of pain conditions. In this pilot study, we investigated the effect of traditional cupping therapy on chronic nonspecific neck pain (CNP) and mechanical sensory thresholds. Methods. Fifty CNP patients were randomly assigned to treatment (TG, n = 25) or waiting list control group (WL, n = 25). TG received a single cupping treatment. Pain at rest (PR), pain related to movement (PM), quality of life (SF-36), Neck Disability Index (NDI), mechanical detection (MDT), vibration detection (MDT), and pressure pain thresholds (PPT) were measured before and three days after a single cupping treatment. Patients also kept a pain and medication diary (PaDi, MeDi) during the study. Results. Baseline characteristics were similar in the two groups. After cupping TG reported significantly less pain (PR: -17.9 mm VAS, 95%CI -29.2 to -6.6; PM: -19.7, 95%CI -32.2 to -7.2; PaDi: -1.5 points on NRS, 95%CI -2.5 to -0.4; all P cupping might be an effective treatment for improving pain, quality of life, and hyperalgesia in CNP.

  10. Short Term Effects of Mobilization Techniques on Neck Pain and Deep Neck Flexor Muscle Endurance in Patients with Mechanical Chronic Neck Pain

    Science.gov (United States)

    Kılınç, Hasan Erkan; Harput, Gülcan; Baltacı, Gül; İnce, Deniz İnal

    2014-01-01

    Objectives: The aim of the study was to investigate short term effects of cervical and scapular mobilization techniques on neck pain and deep cervical muscles endurance in chronical mechanical neck pain patients. Methods: 22 chronical mechanic neck pain patients four male 18 female (mean age: mean±sd 35.59± 15.85) were included. Before treatment, neck pain level (visual analog scale) and deep neck flexor muscles endurance (in supine position with digital chronometer) of all patients were evaluated. Cyriax cervical mobilization for 10 minutes and scapular mobilization for 10 repetition 10 sets were performed to patients as treatment protocol. After treatment, 24 hours after and a week after evaluations of neck pain and deep cervical muscles endurance were repeated. Results: Before treatment Neck pain Visual Analog Scale scores was 5.78±1.43 point, 2.80±1.99 point after treatment, 24 hours later 3.36±2.12 point, one week later 3.91±2.24 point. This alteration was found significant statistically (p<0.01). Before treatment deep cervical flexor muscle endurance score was 27.25±17.74 sec, after treatment 39.46±25.20 sec, 24 hours later 38.67±28.43 and one week later 40.11±27.82 sec. This alteration was also found significant statistically (p=0.01). Conclusion: Initially neck pain scores in our subjects decreased quickly, after 24 hours these scores increased but last scores were below first neck pain level in a week follow-up. Deep neck cervical flexor muscles test scores also increased quickly, after 24 hours later this scores were stable along a week. Mobilization techniques are effective methods on neck pain and endurance in chronical mechanic neck pain patients.

  11. Dissociable neural mechanisms underlying the modulation of pain and anxiety? An FMRI pilot study.

    Science.gov (United States)

    Wiech, Katja; Edwards, Robert; Moseley, Graham Lorimer; Berna, Chantal; Ploner, Markus; Tracey, Irene

    2014-01-01

    The down-regulation of pain through beliefs is commonly discussed as a form of emotion regulation. In line with this interpretation, the analgesic effect has been shown to co-occur with reduced anxiety and increased activity in the ventrolateral prefrontal cortex (VLPFC), which is a key region of emotion regulation. This link between pain and anxiety modulation raises the question whether the two effects are rooted in the same neural mechanism. In this pilot fMRI study, we compared the neural basis of the analgesic and anxiolytic effect of two types of threat modulation: a "behavioral control" paradigm, which involves the ability to terminate a noxious stimulus, and a "safety signaling" paradigm, which involves visual cues that signal the threat (or absence of threat) that a subsequent noxious stimulus might be of unusually high intensity. Analgesia was paralleled by VLPFC activity during behavioral control. Safety signaling engaged elements of the descending pain control system, including the rostral anterior cingulate cortex that showed increased functional connectivity with the periaqueductal gray and VLPFC. Anxiety reduction, in contrast, scaled with dorsolateral prefrontal cortex activation during behavioral control but had no distinct neural signature during safety signaling. Our pilot data therefore suggest that analgesic and anxiolytic effects are instantiated in distinguishable neural mechanisms and differ between distinct stress- and pain-modulatory approaches, supporting the recent notion of multiple pathways subserving top-down modulation of the pain experience. Additional studies in larger cohorts are needed to follow up on these preliminary findings.

  12. Dissociable neural mechanisms underlying the modulation of pain and anxiety? An FMRI pilot study.

    Directory of Open Access Journals (Sweden)

    Katja Wiech

    Full Text Available The down-regulation of pain through beliefs is commonly discussed as a form of emotion regulation. In line with this interpretation, the analgesic effect has been shown to co-occur with reduced anxiety and increased activity in the ventrolateral prefrontal cortex (VLPFC, which is a key region of emotion regulation. This link between pain and anxiety modulation raises the question whether the two effects are rooted in the same neural mechanism. In this pilot fMRI study, we compared the neural basis of the analgesic and anxiolytic effect of two types of threat modulation: a "behavioral control" paradigm, which involves the ability to terminate a noxious stimulus, and a "safety signaling" paradigm, which involves visual cues that signal the threat (or absence of threat that a subsequent noxious stimulus might be of unusually high intensity. Analgesia was paralleled by VLPFC activity during behavioral control. Safety signaling engaged elements of the descending pain control system, including the rostral anterior cingulate cortex that showed increased functional connectivity with the periaqueductal gray and VLPFC. Anxiety reduction, in contrast, scaled with dorsolateral prefrontal cortex activation during behavioral control but had no distinct neural signature during safety signaling. Our pilot data therefore suggest that analgesic and anxiolytic effects are instantiated in distinguishable neural mechanisms and differ between distinct stress- and pain-modulatory approaches, supporting the recent notion of multiple pathways subserving top-down modulation of the pain experience. Additional studies in larger cohorts are needed to follow up on these preliminary findings.

  13. Persistent facial pain conditions

    DEFF Research Database (Denmark)

    Forssell, Heli; Alstergren, Per; Bakke, Merete

    2016-01-01

    , clinical features, consequences, central and peripheral mechanisms, diagnostic criteria (DC/TMD), and principles of management. For each of the neuropathic facial pain entities, the definitions, prevalence, clinical features, and diagnostics are described. The current understanding of the pathophysiology......Persistent facial pains, especially temporomandibular disorders (TMD), are common conditions. As dentists are responsible for the treatment of most of these disorders, up-to date knowledge on the latest advances in the field is essential for successful diagnosis and management. The review covers...... TMD, and different neuropathic or putative neuropathic facial pains such as persistent idiopathic facial pain and atypical odontalgia, trigeminal neuralgia and painful posttraumatic trigeminal neuropathy. The article presents an overview of TMD pain as a biopsychosocial condition, its prevalence...

  14. Cumulative mechanical low-back load at work is a determinant of low-back pain

    NARCIS (Netherlands)

    Coenen, P.; Kingma, I.; Boot, C.R.L.; Bongers, P.M.; Dieën, J.H. van

    2014-01-01

    Objectives: Reported associations of physical exposures during work (eg, lifting, trunk flexion or rotation) and low-back pain (LBP) are rather inconsistent. Mechanical back loads (eg, moments on the low back) as a result of exposure to abovementioned risk factors have been suggested to be important

  15. Pulsed radiofrequency treatment in interventional pain management: mechanisms and potential indications-a review

    NARCIS (Netherlands)

    Chua Hai Liang, N.; Vissers, K.C.P.; Sluijter, M.E.

    2011-01-01

    BACKGROUND: The objective of this review is to evaluate the efficacy of Pulsed Radiofrequency (PRF) treatment in chronic pain management in randomized clinical trials (RCTs) and well-designed observational studies. The physics, mechanisms of action, and biological effects are discussed to provide th

  16. Central Effect of Exogenous Histamine on Pain Induced by Sub-Plantar Injection of Formalin in Rabbits

    Directory of Open Access Journals (Sweden)

    Esmaeal Tamaddonfard

    2010-06-01

    Full Text Available In the present study, the effects of intracerebroventricular (ICV administration of normal saline (control, histamine, mepyramine (a histamine H1-receptor antagonist and ranitidine (a histamine H2-receptor antagonist were investigated on the formalin-induced pain in rabbits. Subcutaneous (SC injection of a formalin (100 μl, 5% solution into the ventral surface of the right hind paw was performed, and the time durations spent licking and biting the injected paw were measured in 10 min blocks for 1 h. The SC injection of formalin produced a short-lasting (10 min pain response. The ICV injection of histamine at doses of 25, 50 and 100 μg significantly (P < 0.05 decreased the time duration spent licking and biting the injected paw. Mepyramine and ranitidine, used alone produced no effects. The ICV pretreatments with mepyramine and ranitidine at the same dose of 200 μg significantly (P < 0.05 prevented histamine (100 μg, ICV-induced antinociception. These results indicate that activation of brain histamine with ICV injection of exogenous histamine produces antinociception. Central histamine H1 and H2 receptors may be involved in the centrally administered histamine-induced antinociception in the formalin-induced pain in rabbits.

  17. A possible central mechanism in autism spectrum disorders, part 1.

    Science.gov (United States)

    Blaylock, Russell L

    2008-01-01

    The autism spectrum disorders (ASD) are a group of related neurodevelopmental disorders that have been increasing in incidence since the 1980s. Despite a considerable amount of data being collected from cases, a central mechanism has not been offered. A careful review of ASD cases discloses a number of events that adhere to an immunoexcitotoxic mechanism. This mechanism explains the link between excessive vaccination, use of aluminum and ethylmercury as vaccine adjuvants, food allergies, gut dysbiosis, and abnormal formation of the developing brain. It has now been shown that chronic microglial activation is present in autistic brains from age 5 years to age 44 years. A considerable amount of evidence, both experimental and clinical, indicates that repeated microglial activation can initiate priming of the microglia and that subsequent stimulation can produce an exaggerated microglial response that can be prolonged. It is also known that one phenotypic form of microglia activation can result in an outpouring of neurotoxic levels of the excitotoxins, glutamate and quinolinic acid. Studies have shown that careful control of brain glutamate levels is essential to brain pathway development and that excesses can result in arrest of neural migration, as well as dendritic and synaptic loss. It has also been shown that certain cytokines, such as TNF-alpha, can, via its receptor, interact with glutamate receptors to enhance the neurotoxic reaction. To describe this interaction I have coined the term immunoexcitotoxicity, which is described in this article.

  18. Cortical Mechanisms of Central Fatigue and Sense of Effort.

    Directory of Open Access Journals (Sweden)

    Simon A Sharples

    Full Text Available The purpose of this study was to investigate cortical mechanisms upstream to the corticospinal motor neuron that may be associated with central fatigue and sense of effort during and after a fatigue task. We used two different isometric finger abduction protocols to examine the effects of muscle activation and fatigue the right first dorsal interosseous (FDI of 12 participants. One protocol was intended to assess the effects of muscle activation with minimal fatigue (control and the other was intended to elicit central fatigue (fatigue. We hypothesized that high frequency repetitive transcranial magnetic stimulation (rTMS of the supplementary motor area (SMA would hasten recovery from central fatigue and offset a fatigue-induced increase in sense of effort by facilitating the primary motor cortex (M1. Constant force-sensation contractions were used to assess sense of effort associated with muscle contraction. Paired-pulse TMS was used to assess intracortical inhibition (ICI and facilitation (ICF in the active M1 and interhemispheric inhibitory (IHI was assessed to determine if compensation occurs via the resting M1. These measures were made during and after the muscle contraction protocols. Corticospinal excitability progressively declined with fatigue in the active hemisphere. ICF increased at task failure and ICI was also reduced at task failure with no changes in IHI found. Although fatigue is associated with progressive reductions in corticospinal excitability, compensatory changes in inhibition and facilitation may act within, but not between hemispheres of the M1. rTMS of the SMA following fatigue enhanced recovery of maximal voluntary force and higher levels of ICF were associated with lower sense of effort following stimulation. rTMS of the SMA may have reduced the amount of upstream drive required to maintain motor output, thus contributing to a lower sense of effort and increased rate of recovery of maximal force.

  19. Cortical Mechanisms of Central Fatigue and Sense of Effort.

    Science.gov (United States)

    Sharples, Simon A; Gould, Jason A; Vandenberk, Michael S; Kalmar, Jayne M

    2016-01-01

    The purpose of this study was to investigate cortical mechanisms upstream to the corticospinal motor neuron that may be associated with central fatigue and sense of effort during and after a fatigue task. We used two different isometric finger abduction protocols to examine the effects of muscle activation and fatigue the right first dorsal interosseous (FDI) of 12 participants. One protocol was intended to assess the effects of muscle activation with minimal fatigue (control) and the other was intended to elicit central fatigue (fatigue). We hypothesized that high frequency repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area (SMA) would hasten recovery from central fatigue and offset a fatigue-induced increase in sense of effort by facilitating the primary motor cortex (M1). Constant force-sensation contractions were used to assess sense of effort associated with muscle contraction. Paired-pulse TMS was used to assess intracortical inhibition (ICI) and facilitation (ICF) in the active M1 and interhemispheric inhibitory (IHI) was assessed to determine if compensation occurs via the resting M1. These measures were made during and after the muscle contraction protocols. Corticospinal excitability progressively declined with fatigue in the active hemisphere. ICF increased at task failure and ICI was also reduced at task failure with no changes in IHI found. Although fatigue is associated with progressive reductions in corticospinal excitability, compensatory changes in inhibition and facilitation may act within, but not between hemispheres of the M1. rTMS of the SMA following fatigue enhanced recovery of maximal voluntary force and higher levels of ICF were associated with lower sense of effort following stimulation. rTMS of the SMA may have reduced the amount of upstream drive required to maintain motor output, thus contributing to a lower sense of effort and increased rate of recovery of maximal force.

  20. Distinct TRPV1- and TRPA1-based mechanisms underlying enhancement of oral ulcerative mucositis-induced pain by 5-fluorouracil.

    Science.gov (United States)

    Yamaguchi, Kiichiro; Ono, Kentaro; Hitomi, Suzuro; Ito, Misa; Nodai, Tomotaka; Goto, Tetsuya; Harano, Nozomu; Watanabe, Seiji; Inoue, Hiromasa; Miyano, Kanako; Uezono, Yasuhito; Matoba, Motohiro; Inenaga, Kiyotoshi

    2016-05-01

    In many patients with cancer, chemotherapy-induced severe oral ulcerative mucositis causes intractable pain, leading to delays and interruptions in therapy. However, the pain mechanism in oral ulcerative mucositis after chemotherapy has not been extensively studied. In this study, we investigated spontaneous pain and mechanical allodynia in a preclinical model of oral ulcerative mucositis after systemic administration of the chemotherapy drug 5-fluorouracil, using our proprietary pain assay system for conscious rats. 5-Fluorouracil caused leukopenia but did not induce pain-related behaviors. After 5-fluorouracil administration, oral ulcers were developed with topical acetic acid treatment. Compared with saline-treated rats, 5-fluorouracil-exposed rats showed more severe mucositis with excessive bacterial loading due to a lack of leukocyte infiltration, as well as enhancements of spontaneous pain and mechanical allodynia. Antibacterial drugs, the lipid A inhibitor polymyxin B and the TRPV1/TRPA1 channel pore-passing anesthetic QX-314, suppressed both the spontaneous pain and the mechanical allodynia. The cyclooxygenase inhibitor indomethacin and the TRPV1 antagonist SB-366791 inhibited the spontaneous pain, but not the mechanical allodynia. In contrast, the TRPA1 antagonist HC-030031 and the N-formylmethionine receptor FPR1 antagonist Boc MLF primarily suppressed the mechanical allodynia. These results suggest that 5-fluorouracil-associated leukopenia allows excessive oral bacterial infection in the oral ulcerative region, resulting in the enhancement of spontaneous pain through continuous TRPV1 activation and cyclooxygenase pathway, and mechanical allodynia through mechanical sensitization of TRPA1 caused by neuronal effects of bacterial toxins. These distinct pain mechanisms explain the difficulties encountered with general treatments for oral ulcerative mucositis-induced pain in patients with cancer and suggest more effective approaches.

  1. Pricing Mechanism Design for Centralized Pollutant Treatment with SME Alliances.

    Science.gov (United States)

    Li, Yuyu; Huang, Bo; Tao, Fengming

    2016-06-22

    In this paper, we assume that a professional pollutant treatment enterprise treats all of the pollutants emitted by multiple small and medium-sized enterprises (SMEs). In order to determine the treatment price, SMEs can bargain with the pollutant treatment enterprise individually, or through forming alliances. We propose a bargaining game model of centralized pollutant treatment to study how the pollutant treatment price is determined through negotiation. Then, we consider that there is a moral hazard from SMEs in centralized pollutant treatment; in other words, they may break their agreement concerning their quantities of production and pollutant emissions with the pollutant treatment enterprise. We study how the pollutant treatment enterprise can prevent this by pricing mechanism design. It is found that the pollutant treatment enterprise can prevent SMEs' moral hazard through tiered pricing. If the marginal treatment cost of the pollutant treatment enterprise is a constant, SMEs could bargain with the pollutant treatment enterprise individually, otherwise, they should form a grand alliance to bargain with it as a whole.

  2. Mechanical Diagnosis and Therapy has similar effects on pain and disability as ‘wait and see’ and other approaches in people with neck pain: a systematic review

    Directory of Open Access Journals (Sweden)

    Hiroshi Takasaki

    2014-06-01

    Full Text Available Questions: In people with neck pain, does Mechanical Diagnosis and Therapy (MDT reduce pain and disability more than ‘wait and see’? Does MDT reduce pain and disability more than other interventions? Are any differences in effect clinically important? Design: Systematic review of randomised trials with meta-analysis. Participants: People with neck pain. Intervention: MDT. Outcome measures: Pain intensity and disability due to neck pain in the short (< 3 months, intermediate (< 1 year and long term (≥ 1 year. Results: Five trials were included. Most comparisons demonstrated mean differences in effect that favoured MDT over wait-and-see controls or other interventions, although most were statistically non-significant. For pain, all comparisons had a 95% confidence interval (CI with lower limits that were less than 20 on a scale of 0 to 100, which suggests that the difference may not be clinically important. For disability, even the upper limits of the 95% CI were below this threshold, confirming that the differences are not clinically important. In all of the trials, some or all of the treating therapists did not have the highest level of MDT training. Conclusion: The additional benefit of MDT compared with the wait-and-see approach or other therapeutic approaches may not be clinically important in terms of pain intensity and is not clinically important in terms of disability. However, these estimates of the effect of MDT may reflect suboptimal training of the treating therapists. Further research could improve the precision of the estimates and assess whether the extent of training in MDT influences its effect. [Takasaki H, May S (2014 Mechanical Diagnosis and Therapy has similar effects on pain and disability as ‘wait and see’ and other approaches in people with neck pain: a systematic review. Journal of Physiotherapy 60: 78–84].

  3. Dor central devida a compressão do cortex parietal por tumor cerebral: relato de dois casos Central pain from cerebral cortical parietal tumors: report of two cases

    Directory of Open Access Journals (Sweden)

    Edson José Amâncio

    2002-06-01

    Full Text Available Dor central produzida por tumores cerebrais é considerada rara pela maioria dos autores. Os poucos casos descritos na literatura fazem referência à dor central provocada pela presença de lesões expansivas acometendo o córtex parietal contralateral. Nem mesmo os tumores talâmicos costumam produzir dor central. Apresentamos dois casos de dor central associada a lesões expansivas que acometeram o córtex parietal, 1 astrocitoma low grade e 1 meningioma. Em ambos houve alívio da dor após a remoção cirúrgica das lesões.Central pain derived from cerebral tumors is considered rare by most authors. The few cases described in literature refer to central pain caused by expansive lesions in the contralatral parietal cortex. Usually, not even thalamic tumors cause central pain. We describe two cases of central pain related to expansive lesions in the parietal cortical region -- a low grade astrocytoma and a meningioma. Both patients reported pain relief after lesions were removed by surgery.

  4. Parkinson's disease without tremor masquerading as mechanical back pain; a case report.

    Science.gov (United States)

    Burton, Robert R

    2008-08-01

    The clinical features of a 67-year-old female suffering recurrent low back pain (LBP) who developed Parkinson's disease (PD) are presented. PD is a progressive, age-specific neuro-degenerative disorder characterized by a combination of bradykinesia (slowness of movement), rest tremor (initially unilaterally and usually of the hands), rigidity or stiffness of the arms, legs or neck, and/or postural instability. Other non-motor and cognitive symptoms may accompany these features. Tremor, at rest, is usually the earliest and most prominent cardinal symptom of PD, but is absent in approximately 30% of patients. Considering mechanical back pain commonly presents with slowed movement and gait disturbance due to pain avoidance behavior, and considering Canada's population is aging and living longer will inevitably cause the number of Parkinson's patients to increase, it is important for chiropractic doctors to maintain an awareness of the condition to facilitate its early referral, diagnosis and management.

  5. Untangling nociceptive, neuropathic and neuroplastic mechanisms underlying the biological domain of back pain.

    Science.gov (United States)

    Hush, Julia M; Stanton, Tasha R; Siddall, Philip; Marcuzzi, Anna; Attal, Nadine

    2013-05-01

    SUMMARY Current clinical practice guidelines advocate a model of diagnostic triage for back pain, underpinned by the biopsychosocial paradigm. However, limitations of this clinical model have become apparent: it can be difficult to classify patients into the diagnostic triage categories; patients with 'nonspecific back pain' are clearly not a homogenous group; and mean effects of treatments based on this approach are small. In this article, it is proposed that the biological domain of the biopsychosocial model needs to be reconceptualized using a neurobiological mechanism-based approach. Recent evidence about nociceptive and neuropathic contributors to back pain is outlined in the context of maladaptive neuroplastic changes of the somatosensory system. Implications for clinical practice and research are discussed.

  6. Antihyperalgesic and antiallodynic effects of mianserin on diabetic neuropathic pain: a study on mechanism of action.

    Science.gov (United States)

    Üçel, Umut İrfan; Can, Özgür Devrim; Demir Özkay, Ümide; Öztürk, Yusuf

    2015-06-05

    This study used various experimental pain methods to investigate the effects of subacute mianserin administration on diabetes-induced neuropathic pain in rats. The effect of mianserin on hyperalgesia occurring in connection with peripheral diabetic neuropathy was examined using the Randall-Selitto (mechanical nociceptive stimulus), Hargreaves (thermal nociceptive stimulus), and cold-plate (4°C, thermal nociceptive stimulus) tests. The dynamic plantar aesthesiometer, which measures the threshold values for mechanical stimuli, was used for allodynia studies. Thermal allodynia was evaluated with the warm-plate (38°C) test. At 30 and 45 mg/kg, mianserin effectively improved mechanical and thermal hyperalgesia occurring in connection with diabetic neuropathy. Subacute administration of mianserin also reduced diabetes-associated mechanical and thermal allodynia. The ability of mianserin to reduce diabetic neuropathic pain was comparable to that of pregabalin (10mg/kg). The antihyperalgesic and antiallodynic effects of mianserin were reversed with α-methyl-para-tyrosine methyl ester (AMPT, an inhibitor of catecholamine synthesis), phentolamine (a non-selective α-adrenoceptor antagonist), propranolol (a non-selective β-adrenoceptor antagonist), and naloxone (a non-selective opioid receptor antagonist) administrations. The same effects were not reversed, however, by para-chlorophenylalanine methyl ester (PCPA; an inhibitor of serotonin synthesis). These results suggest that the beneficial effect of mianserin on diabetic neuropathic pain is mediated through an increase in catecholamine levels in the synaptic cleft as well as through interactions with both subtypes of adrenoceptors and opioid receptors. Considering that mianserin exhibits simultaneous antidepressant and antinociceptive effects, this drug could provide a good alternative for treating the pain associated with diabetic neuropathy and the mood disorders caused directly by diabetes.

  7. Electromagnetic Field Devices and Their Effects on Nociception and Peripheral Inflammatory Pain Mechanisms.

    Science.gov (United States)

    Ross, Christina L; Teli, Thaleia; Harrison, Benjamin S

    2016-03-01

    Context • During cell-communication processes, endogenous and exogenous signaling affects normal and pathological developmental conditions. Exogenous influences, such as extra-low-frequency (ELF) electromagnetic fields (EMFs) have been shown to affect pain and inflammation by modulating G-protein coupling receptors (GPCRs), downregulating cyclooxygenase-2 (Cox-2) activity, and downregulating inflammatory modulators, such as tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) as well as the transcription factor nuclear factor kappa B (NF-κB). EMF devices could help clinicians who seek an alternative or complementary treatment for relief of patients chronic pain and disability. Objective • The research team intended to review the literature on the effects of EMFs on inflammatory pain mechanisms. Design • We used a literature search of articles published in PubMed using the following key words: low-frequency electromagnetic field therapy, inflammatory pain markers, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), opioid receptors, G-protein coupling receptors, and enzymes. Setting • The study took place at the Wake Forest School of Medicine in Winston-Salem, NC, USA. Results • The mechanistic pathway most often considered for the biological effects of EMF is the plasma membrane, across which the EMF signal induces a voltage change. Oscillating EMF exerts forces on free ions that are present on both sides of the plasma membrane and that move across the cell surface through transmembrane proteins. The ions create a forced intracellular vibration that is responsible for phenomena such as the influx of extracellular calcium (Ca2+) and the binding affinity of calmodulin (CaM), which is the primary transduction pathway to the secondary messengers, cAMP and cGMP, which have been found to influence inflammatory pain. Conclusions • An emerging body of evidence indicates the existence of a frequency

  8. Psychological pain interventions and neurophysiology: implications for a mechanism-based approach.

    Science.gov (United States)

    Flor, Herta

    2014-01-01

    This article provides an illustrative overview of neurophysiological changes related to acute and chronic pain involving structural and functional brain changes, which might be the targets of psychological interventions. A number of psychological pain treatments have been examined with respect to their effects on brain activity, ranging from cognitive- and operant behavioral interventions, meditation and hypnosis, to neuro- and biofeedback, discrimination training, imagery and mirror treatment, as well as virtual reality and placebo applications. These treatments affect both ascending and descending aspects of pain processing and act through brain mechanisms that involve sensorimotor areas as well as those involved in affective-motivational and cognitive-evaluative aspects. The analysis of neurophysiological changes related to effective psychological pain treatment can help to identify subgroups of patients with chronic pain who might profit from different interventions, can aid in predicting treatment outcome, and can assist in identifying responders and nonresponders, thus enhancing the efficacy and efficiency of psychological interventions. Moreover, new treatment targets can be developed and tested. Finally, the use of neurophysiological measures can also aid in motivating patients to participate in psychological interventions and can increase their acceptance in clinical practice.

  9. Case studies in cervicothoracic spine function evaluation and treatment of two dancers with mechanical neck pain.

    Science.gov (United States)

    Sandow, Emily

    2011-03-01

    It has been reported that manual therapy directed at the thoracic spine followed by exercise may improve outcomes in patients with mechanical neck pain. At this point, there is little available data on dancers with neck pain, and it is unclear whether this type of treatment is appropriate for restoring the rigorous level of activity required of the dancer. The purpose of this study was to review the evaluation, clinical decision-making process, and treatment of two dancers-one with acute and the other with chronic neck pain-who fell into the classification of patients who might benefit from an intervention to the thoracic spine. The two participants were a musical theater dancer with an acute onset of neck pain and a retired dancer who was an active dance company director with an 11-year history of chronic neck pain. Both participants went through a standard examination and were treated with mobilizations to the upper thoracic spine followed by therapeutic exercises. In both cases, successful outcomes were achieved immediately after treatment and up to six months after discharge from physical therapy.

  10. Central projection of pain arising from delayed onset muscle soreness (DOMS in human subjects.

    Directory of Open Access Journals (Sweden)

    Katharina Zimmermann

    Full Text Available Delayed onset muscle soreness (DOMS is a subacute pain state arising 24-48 hours after a bout of unaccustomed eccentric muscle contractions. Functional magnetic resonance imaging (fMRI was used to examine the patterns of cortical activation arising during DOMS-related pain in the quadriceps muscle of healthy volunteers evoked by either voluntary contraction or physical stimulation. The painful movement or physical stimulation of the DOMS-affected thigh disclosed widespread activation in the primary somatosensory and motor (S1, M1 cortices, stretching far beyond the corresponding areas somatotopically related to contraction or physical stimulation of the thigh; activation also included a large area within the cingulate cortex encompassing posteroanterior regions and the cingulate motor area. Pain-related activations were also found in premotor (M2 areas, bilateral in the insular cortex and the thalamic nuclei. In contrast, movement of a DOMS-affected limb led also to activation in the ipsilateral anterior cerebellum, while DOMS-related pain evoked by physical stimulation devoid of limb movement did not.

  11. Central Projection of Pain Arising from Delayed Onset Muscle Soreness (DOMS) in Human Subjects

    Science.gov (United States)

    Zimmermann, Katharina; Leidl, Caroline; Kaschka, Miriam; Carr, Richard W.; Terekhin, Pavel; Handwerker, Hermann O.; Forster, Clemens

    2012-01-01

    Delayed onset muscle soreness (DOMS) is a subacute pain state arising 24–48 hours after a bout of unaccustomed eccentric muscle contractions. Functional magnetic resonance imaging (fMRI) was used to examine the patterns of cortical activation arising during DOMS-related pain in the quadriceps muscle of healthy volunteers evoked by either voluntary contraction or physical stimulation. The painful movement or physical stimulation of the DOMS-affected thigh disclosed widespread activation in the primary somatosensory and motor (S1, M1) cortices, stretching far beyond the corresponding areas somatotopically related to contraction or physical stimulation of the thigh; activation also included a large area within the cingulate cortex encompassing posteroanterior regions and the cingulate motor area. Pain-related activations were also found in premotor (M2) areas, bilateral in the insular cortex and the thalamic nuclei. In contrast, movement of a DOMS-affected limb led also to activation in the ipsilateral anterior cerebellum, while DOMS-related pain evoked by physical stimulation devoid of limb movement did not. PMID:23056613

  12. Pregabalin in patients with central neuropathic pain: a randomized, double-blind, placebo-controlled trial of a flexible-dose regimen.

    Science.gov (United States)

    Vranken, J H; Dijkgraaf, M G W; Kruis, M R; van der Vegt, M H; Hollmann, M W; Heesen, M

    2008-05-01

    The effective treatment of patients suffering from central neuropathic pain remains a clinical challenge, despite a standard pharmacological approach in combination with anticonvulsants and antidepressants. A randomized, double-blinded, placebo-controlled trial evaluated the effects of pregabalin on pain relief, tolerability, health status, and quality of life in patients with central neuropathic pain caused by brain or spinal cord injuries. At baseline and 4 weeks after the start of treatment subjects were evaluated with standard measures of efficacy: pain intensity measured by visual analog scale, health status (Pain Disability Index and EQ-5D) and quality of life (SF-36). Forty patients received escalating doses of either pregabalin (150, 300, and 600mg/day) or matching placebo capsules. In both groups, patients started with 1 capsule per day (either 150mg of pregabalin or placebo). If pain relief was insufficient, patients were titrated to a higher dose. There was a statistically significant decrease in mean pain score at endpoint for pregabalin treatment, compared with placebo (P=0.016). Follow-up observation showed no significant difference in Pain Disability Index scores between the two groups. The pregabalin group, however, showed a statistically significant improvement for the EQ-5D. Pregabalin treatment led to a significant improvement in the bodily pain domain of the SF36. In the other domains, more favorable scores were reported without reaching statistical significance. Pregabalin, in a flexible-dose regime, produced clinically significant reductions in pain, as well as improvements in health status in patients suffering from severe central neuropathic pain.

  13. Pain-related increase of excitatory transmission and decrease of inhibitory transmission in the central nucleus of the amygdala are mediated by mGluR1

    Directory of Open Access Journals (Sweden)

    Neugebauer Volker

    2010-12-01

    Full Text Available Abstract Neuroplasticity in the central nucleus of the amygdala (CeA, particularly its latero-capsular division (CeLC, is an important contributor to the emotional-affective aspects of pain. Previous studies showed synaptic plasticity of excitatory transmission to the CeLC in different pain models, but pain-related changes of inhibitory transmission remain to be determined. The CeLC receives convergent excitatory inputs from the parabrachial nucleus in the brainstem and from the basolateral amygdala (BLA. In addition, feedforward inhibition of CeA neurons is driven by glutamatergic projections from the BLA area to a cluster of GABAergic neurons in the intercalated cell masses (ITC. Using patch-clamp in rat brain slices we measured monosynaptic excitatory postsynaptic currents (EPSCs and polysynaptic inhibitory currents (IPSCs that were evoked by electrical stimulation in the BLA. In brain slices from arthritic rats, input-output functions of excitatory synaptic transmission were enhanced whereas inhibitory synaptic transmission was decreased compared to control slices from normal untreated rats. A non-NMDA receptor antagonist (NBQX blocked the EPSCs and reduced the IPSCs, suggesting that non-NMDA receptors mediate excitatory transmission and also contribute to glutamate-driven feed-forward inhibition of CeLC neurons. IPSCs were blocked by a GABAA receptor antagonist (bicuculline. Bicuculline increased EPSCs under normal conditions but not in slices from arthritic rats, which indicates a loss of GABAergic control of excitatory transmission. A metabotropic glutamate receptor subtype 1 (mGluR1 antagonist (LY367385 reversed both the increase of excitatory transmission and the decrease of inhibitory transmission in the arthritis pain model but had no effect on basal synaptic transmission in control slices from normal rats. The inhibitory effect of LY367385 on excitatory transmission was blocked by bicuculline suggesting the involvement of a GABAergic

  14. Prevalence and proposed mechanisms of chronic low back pain in baseball: part i.

    Science.gov (United States)

    Wasser, Joseph G; Zaremski, Jason L; Herman, Daniel C; Vincent, Heather K

    2017-01-27

    The prevalence of low back pain (LBP) among active baseball players ranges between 3 and 15%. The execution of baseball-specific manoeuvres, such as pitching or batting, may be related to the onset of LBP. These baseball motions are complex and require appropriate activation of the core musculature to produce a well-timed motion with forces minimized at the extremities. The spine, core and back musculature are involved with acceleration and deceleration of rotational motions. This narrative review synopsizes the available evidence of the prevalence of and mechanical factors underlying LBP in the baseball population. Possible mechanical mechanisms linking baseball play to LBP include aberrant motion, improper timing, high lumbar stress due to mechanical loading and lumbopelvic strength deficits. Potential clinical implications relating to these possible mechanical mechanisms will also be highlighted. The state of the evidence suggests that there are deficits in understanding the role of baseball motion and playing history in the development of spine conditions.

  15. The Effect of Traditional Cupping on Pain and Mechanical Thresholds in Patients with Chronic Nonspecific Neck Pain: A Randomised Controlled Pilot Study

    Directory of Open Access Journals (Sweden)

    Romy Lauche

    2012-01-01

    Full Text Available Introduction. Cupping has been used since antiquity in the treatment of pain conditions. In this pilot study, we investigated the effect of traditional cupping therapy on chronic nonspecific neck pain (CNP and mechanical sensory thresholds. Methods. Fifty CNP patients were randomly assigned to treatment (TG, n=25 or waiting list control group (WL, n=25. TG received a single cupping treatment. Pain at rest (PR, pain related to movement (PM, quality of life (SF-36, Neck Disability Index (NDI, mechanical detection (MDT, vibration detection (MDT, and pressure pain thresholds (PPT were measured before and three days after a single cupping treatment. Patients also kept a pain and medication diary (PaDi, MeDi during the study. Results. Baseline characteristics were similar in the two groups. After cupping TG reported significantly less pain (PR: −17.9 mm VAS, 95%CI −29.2 to −6.6; PM: −19.7, 95%CI −32.2 to −7.2; PaDi: −1.5 points on NRS, 95%CI −2.5 to −0.4; all P<0.05 and higher quality of life than WL (SF-36, Physical Functioning: 7.5, 95%CI 1.4 to 13.5; Bodily Pain: 14.9, 95%CI 4.4 to 25.4; Physical Component Score: 5.0, 95%CI 1.4 to 8.5; all P<0.05. No significant effect was found for NDI, MDT, or VDT, but TG showed significantly higher PPT at pain-areas than WL (in lg(kPa; pain-maximum: 0.088, 95%CI 0.029 to 0.148, pain-adjacent: 0.118, 95%CI 0.038 to 0.199; both P<0.01. Conclusion. A single application of traditional cupping might be an effective treatment for improving pain, quality of life, and hyperalgesia in CNP.

  16. Should we abandon cervical spine manipulation for mechanical neck pain? : yes

    OpenAIRE

    2012-01-01

    Cervical spine manipulation (a high velocity, low amplitude, end range thrust manoeuvre) is a common\\ud treatment option for mechanical neck pain yet may carry the potential for serious neurovascular\\ud complications, specifically vertebral artery dissection and subsequent vertebrobasilar stroke. The nonsuperiority\\ud of manipulation to alternative treatments, coupled with concerns regarding safety, renders\\ud cervical spine manipulation unnecessary and inadvisable.

  17. Pulsed radiofrequency treatment in interventional pain management: mechanisms and potential indications—a review

    OpenAIRE

    Chua, Nicholas H L; Kris C Vissers; Sluijter, Menno E.

    2010-01-01

    Background The objective of this review is to evaluate the efficacy of Pulsed Radiofrequency (PRF) treatment in chronic pain management in randomized clinical trials (RCTs) and well-designed observational studies. The physics, mechanisms of action, and biological effects are discussed to provide the scientific basis for this promising modality. Methods We systematically searched for clinical studies on PRF. We searched the MEDLINE (PubMed) and EMBASE database, using the free text terms: pulse...

  18. Effect of dexmedetomidine on mechanical pain threshold and emergence agitation after laparoscopic myomectomy

    Institute of Scientific and Technical Information of China (English)

    Tao Qin; Xiao-Mei Liu

    2016-01-01

    Objective:To study the effect of dexmedetomidine on mechanical pain threshold and emergence agitation after laparoscopic myomectomy.Methods:Random number table was used to divide 82 cases of patients who received laparoscopic myomectomy in our hospital from May 2012 to October 2014 into dexmedetomidine group (Dex group) and control group (Con group), and postoperative mechanical pain threshold and emergence agitation extent were assessed.Results: 4 h, 8 h, 12 h and 24 h after operation, mechanical pain threshold of both Dex group and Con group were significantly lower than those before operation (P<0.05) and mechanical pain threshold of Dex group 4 h, 8 h, 12 h and 24 h after operation were significantly higher than those of Con group (P<0.05); both incidence and average grade of emergence agitation of Dex group were significantly lower than those of Con group (P<0.05); serum melatonin content of Dex group in recovery period were not significantly different from those in anesthesia induction period, serum melatonin content of Con group in recovery period were significantly lower than those in anesthesia induction period, and serum melatonin content of Dex group in recovery period were significantly higher than those of Con group (P<0.05); serum cortisol content of both Dex group and Con group in recovery period were significantly higher than those before anesthesia induction and cortisol content of Dex group in recovery period was significantly lower than that of Con group (P<0.05).Conclusions:Dexmedetomidine for laparoscopic myomectomy can reduce postoperative hyperalgesia and prevent emergence agitation, and it has positive clinical value.

  19. Signaling mechanisms regulating myelination in the central nervous system

    Institute of Scientific and Technical Information of China (English)

    Jared T.Ahrendsen; Wendy Macklin

    2013-01-01

    The precise and coordinated production of myelin is essential for proper development and function of the nervous system.Diseases that disrupt myelin,including multiple sclerosis,cause significant functional disability.Current treatment aims to reduce the inflammatory component of the disease,thereby preventing damage resulting from demyelination.However,therapies are not yet available to improve natural repair processes after damage has already occurred.A thorough understanding of the signaling mechanisms that regulate myelin generation will improve our ability to enhance repair.In this review,we summarize the positive and negative regulators of myelination,focusing primarily on central nervous system myelination.Axon-derived signals,extracellular signals from both diffusible factors and the extracellular matrix,and intracellular signaling pathways within myelinating oligodendrocytes are discussed.Much is known about the positive regulators that drive myelination,while less is known about the negative regulators that shift active myelination to myelin maintenance at the appropriate time.Therefore,we also provide new data on potential negative regulators of CNS myelination.

  20. Tetrodotoxin suppresses thermal hyperalgesia and mechanical allodynia in a rat full thickness thermal injury pain model.

    Science.gov (United States)

    Salas, Margaux M; McIntyre, Matthew K; Petz, Lawrence N; Korz, Walter; Wong, Donald; Clifford, John L

    2015-10-21

    Burn injuries have been identified as the primary cause of injury in 5% of U.S. military personnel evacuated from Operations Iraqi Freedom and Enduring Freedom. Severe burn-associated pain is typically treated with opioids such as fentanyl, morphine, and methadone. Side effects of opioids include respiratory depression, cardiac depression, decrease in motor and cognitive function, as well as the development of hyperalgesia, tolerance and dependence. These effects have led us to search for novel analgesics for the treatment of burn-associated pain in wounded combat service members. Tetrodotoxin (TTX) is a selective voltage-gated sodium channel blocker currently in clinical trials as an analgesic. A phase 3 clinical trial for cancer-related pain has been completed and phase 3 clinical trials on chemotherapy-induced neuropathic pain are planned. It has also been shown in mice to inhibit the development of chemotherapy-induced neuropathic pain. TTX was originally identified as a neurotoxin in marine animals but has now been shown to be safe in humans at therapeutic doses. The antinociceptive effects of TTX are thought to be due to inhibition of Na(+) ion influx required for initiation and conduction of nociceptive impulses. One TTX sensitive sodium channel, Nav1.7, has been shown to be essential in lowering the heat pain threshold after burn injuries. To date, the analgesic effect of TTX has not been tested in burn-associated pain. Male Sprague-Dawley rats were subjected to a full thickness thermal injury on the right hind paw. TTX (8 μg/kg) was administered once a day systemically by subcutaneous injection beginning 3 days post thermal injury and continued through 7 days post thermal injury. Thermal hyperalgesia and mechanical allodynia were assessed 60 and 120 min post injection on each day of TTX treatment. TTX significantly reduced thermal hyperalgesia at all days tested and had a less robust, but statistically significant suppressive effect on mechanical

  1. Spatial and temporal activation of spinal glial cells: role of gliopathy in central neuropathic pain following spinal cord injury in rats.

    Science.gov (United States)

    Gwak, Young S; Kang, Jonghoon; Unabia, Geda C; Hulsebosch, Claire E

    2012-04-01

    In the spinal cord, neuron and glial cells actively interact and contribute to neurofunction. Surprisingly, both cell types have similar receptors, transporters and ion channels and also produce similar neurotransmitters and cytokines. The neuroanatomical and neurochemical similarities work synergistically to maintain physiological homeostasis in the normal spinal cord. However, in trauma or disease states, spinal glia become activated, dorsal horn neurons become hyperexcitable contributing to sensitized neuronal-glial circuits. The maladaptive spinal circuits directly affect synaptic excitability, including activation of intracellular downstream cascades that result in enhanced evoked and spontaneous activity in dorsal horn neurons with the result that abnormal pain syndromes develop. Recent literature reported that spinal cord injury produces glial activation in the dorsal horn; however, the majority of glial activation studies after SCI have focused on transient and/or acute time points, from a few hours to 1 month, and peri-lesion sites, a few millimeters rostral and caudal to the lesion site. In addition, thoracic spinal cord injury produces activation of astrocytes and microglia that contributes to dorsal horn neuronal hyperexcitability and central neuropathic pain in above-level, at-level and below-level segments remote from the lesion in the spinal cord. The cellular and molecular events of glial activation are not simple events, rather they are the consequence of a combination of several neurochemical and neurophysiological changes following SCI. The ionic imbalances, neuroinflammation and alterations of cell cycle proteins after SCI are predominant components for neuroanatomical and neurochemical changes that result in glial activation. More importantly, SCI induced release of glutamate, proinflammatory cytokines, ATP, reactive oxygen species (ROS) and neurotrophic factors trigger activation of postsynaptic neuron and glial cells via their own receptors

  2. Central effect of histamine and peripheral effect of histidine on the formalin-induced pain response in mice.

    Science.gov (United States)

    Tamaddonfard, Esmaeal; Rahimi, Saead

    2004-08-01

    /mouse, i.c.v., histamine strongly suppressed both phases of the formalin-induced pain response, particularly the second phase. 8. The results of the present study indicate that: (i) activation of brain histamine produces antinociception in the mouse formalin test; (ii) peripheral loading with a high dose of histidine (1000 mg/kg, i.p.) alone exerts the same effect as that seen following 40 microg/mouse, i.c.v., histamine; and (iii) pretreatment with a high dose of histidine potentiates central histamine-induced antinociception.

  3. Mechanism-based classification and physical therapy management of persons with cancer pain: A prospective case series

    Directory of Open Access Journals (Sweden)

    Senthil P Kumar

    2013-01-01

    Full Text Available Context: Mechanism-based classification (MBC was established with current evidence and physical therapy (PT management methods for both cancer and for noncancer pain. Aims: This study aims to describe the efficacy of MBC-based PT in persons with primary complaints of cancer pain. Settings and Design: A prospective case series of patients who attended the physiotherapy department of a multispecialty university-affiliated teaching hospital. Material and Methods: A total of 24 adults (18 female, 6 male aged 47.5 ± 10.6 years, with primary diagnosis of heterogeneous group of cancer, chief complaints of chronic disabling pain were included in the study on their consent for participation The patients were evaluated and classified on the basis of five predominant mechanisms for pain. Physical therapy interventions were recommended based on mechanisms identified and home program was prescribed with a patient log to ensure compliance. Treatments were given in five consecutive weekly sessions for five weeks each of 30 min duration. Statistical Analysis Used: Pre-post comparisons for pain severity (PS and pain interference (PI subscales of Brief pain inventory-Cancer pain (BPI-CP and, European organization for research and treatment in cancer-quality of life questionnaire (EORTC-QLQ-C30 were done using Wilcoxon signed-rank test at 95% confidence interval using SPSS for Windows version 16.0 (SPSS Inc, Chicago, IL. Results: There were statistically significant ( P < 0.05 reduction in pain severity, pain interference and total BPI-CP scores, and the EORTC-QLQ-C30. Conclusion: MBC-PT was effective for improving BPI-CP and EORTC-QLQ-C30 scores in people with cancer pain.

  4. The Rare Painful Phenomena - Chronic Paroxysmal Hemicrania-tic Syndrome as a Clinically Isolated Syndrome of the Central Nervous System.

    Science.gov (United States)

    Ljubisavljevic, Srdjan; Prazic, Ana; Lazarevic, Miodrag; Stojanov, Dragan; Savic, Dejan; Vojinovic, Slobadan

    2017-02-01

    The association of paroxysmal hemicrania with trigeminal neuralgia (TN) has been described and called paroxysmal hemicrania-tic syndrome (PH-tic). We report the case of a patient diagnosed as having chronic PH-tic (CPH-tic) syndrome as a clinically isolated syndrome of the central nervous system (CNS) (CIS).A forty year old woman was admitted to our hospital suffering from right facial pain for the last 2 years. The attacks were paroxysmal, neuralgiform, consisting of throb-like sensations, which developed spontaneously or were triggered by different stimuli in right facial (maxilar and mandibular) areas. Parallel with those, she felt a throbbing orbital and frontal pain with homolateral autonomic symptoms such as conjunctival injection, lacrimation, and the feeling that the ear on the same side was full. This pain lasted most often between 15 and 20 minutes. Beyond hemifacial hypoesthesia in the region of right maxilar and mandibular nerve, the other neurological finding was normal. Magnetic resonance imaging (MRI) study showed a T2-weighted multiple hyperintense paraventricular lesion and hyperintense lesion in the right trigeminal main sensory nucleus and root inlet, all of them being hypointense on T1-weighted image. All of these lesions were hypointense in gadolinium-enhanced T1-weighted images. Neurophysiological studies of trigeminal nerve (somatosensory evoked potentials and blink reflex) correlated with MRI described lesions. The patient's pain bouts were improved immediately after treatment with indomethacin, and were completely relieved with lamotrigine for a longer period. According to the actual McDonald's criteria, clinical state was defined as CIS which was clinically presented by CPH-tic syndrome.Even though it is a clinical rarity and its etiology is usually idiopathic, CPH-tic syndrome can also be symptomatic. When dealing with symptomatic cases, like the one described here, when causal therapy is not possible due to the nature of the primary

  5. Work and neck pain: a prospective study of psychological, social, and mechanical risk factors.

    Science.gov (United States)

    Christensen, Jan Olav; Knardahl, Stein

    2010-10-01

    To determine the impact of occupational psychological/social and mechanical factors on neck pain, a prospective cohort study with a follow-up period of 2 years was conducted with a sample of Norwegian employees. The following designs were tested: (i) cross-sectional analyses at baseline (n=4569) and follow-up (n=4122), (ii) prospective analyses with baseline predictors, (iii) prospective analyses with average exposure over time [(T1+T2)/2] as predictor, and (iv) prospective analyses with measures of change in exposure from T1 to T2 as predictors. A total of 2419 employees responded to both the baseline and follow-up questionnaire. Data were analyzed using ordinal logistic regression. After adjustment for age, sex, neck pain at T1, and other exposure factors that had been estimated to be confounders, the most consistent risk factors were role conflict (highest OR 2.97, 99% CI: 1.29-6.74) and working with arms raised to or above shoulder level (highest OR 1.37, 99% CI: 1.05-1.78). The most consistent protective factors were empowering leadership (lowest OR 0.53, 99% CI: 0.35-0.81) and decision control (lowest OR 0.60, 99% CI: 0.36-1.00). Hence, psychological and social factors are important precursors of neck pain, along with mechanical factors. Although traditional factors such as quantitative demands and decision control play a part in the etiology of neck pain at work, in this study several new factors emerged as more important.

  6. Mindfulness Meditation-Based Pain Relief Employs Different Neural Mechanisms Than Placebo and Sham Mindfulness Meditation-Induced Analgesia

    OpenAIRE

    Zeidan, Fadel; Emerson, Nichole M.; Farris, Suzan R.; Ray, Jenna N.; Jung, Youngkyoo; McHaffie, John G.; Coghill, Robert C.

    2015-01-01

    Mindfulness meditation reduces pain in experimental and clinical settings. However, it remains unknown whether mindfulness meditation engages pain-relieving mechanisms other than those associated with the placebo effect (e.g., conditioning, psychosocial context, beliefs). To determine whether the analgesic mechanisms of mindfulness meditation are different from placebo, we randomly assigned 75 healthy, human volunteers to 4 d of the following: (1) mindfulness meditation, (2) placebo condition...

  7. Cervical Spondylotic Myelopathy presenting as mechanical neck pain: a case report.

    Science.gov (United States)

    Smith, Benjamin E; Diver, Claire J; Taylor, Alan J

    2014-08-01

    Cervical Spondylotic Myelopathy (CSM) is the most common type of myelopathy in adults over 55 years of age. In the early stages symptoms may include local neck pain and stiffness that might mimic the presentation of non-specific mechanical neck pain (NSMNP). The patient was a 79 year old male, who complained of eight weeks of neck pain. He had been referred for physiotherapy by his family physician with a diagnosis of NSMNP. Initial presentation was consistent with the referral, but further assessment by the physiotherapist revealed findings suggestive of CSM. He was referred for an urgent cervical MRI scan, which revealed myelomalacic changes at C3/4 due to spondylotic changes. The patient was unsuitable for manual therapy intervention and was referred to a spinal orthopaedic surgeon who performed a posterior decompression and stabilisation at C3-C5, 2 months after the initial presentation. This case report highlights the importance of considering CSM in adults over 55 years of age presenting with NSMNP, particularly as the prevalence of both increases with age. It demonstrates the need for health professionals to carry out detailed examination where CSM may be a potential differential diagnosis. Outcomes are less favourable for patients over the age of 70, therefore an urgent surgical opinion was required for this patient. Deterioration of symptoms whilst he awaited surgery demonstrates how missed diagnosis may lead to possible long term spinal cord damage, with potential medico-legal concerns for the therapist.

  8. The persistence of pain behaviors in patients with chronic back pain is independent of pain and psychological factors.

    Science.gov (United States)

    Martel, M O; Thibault, P; Sullivan, M J L

    2010-11-01

    The primary purpose of the present study was to examine the temporal stability of communicative and protective pain behaviors in patients with chronic back pain. The study also examined whether the stability of pain behaviors could be accounted for by patients' levels of pain severity, catastrophizing, or fear of movement. Patients (n=70) were filmed on two separate occasions (i.e., baseline, follow-up) while performing a standardized lifting task designed to elicit pain behaviors. Consistent with previous studies, the results provided evidence for the stability of pain behaviors in patients with chronic pain. The analyses indicated that communicative and protective pain behavior scores did not change significantly from baseline to follow-up. In addition, significant test-retest correlations were found between baseline and follow-up pain behavior scores. The results of hierarchical multiple regression analyses further showed that pain behaviors remained stable over time even when accounting for patients' levels of pain severity. Regression analyses also showed that pain behaviors remained stable when accounting for patients' levels of catastrophizing and fear of movement. Discussion addresses the potential contribution of central neural mechanisms and social environmental reinforcement contingencies to the stability of pain behaviors. The discussion also addresses how treatment interventions specifically aimed at targeting pain behaviors might help to augment the overall impact of pain and disability management programs.

  9. Cervical spine osteoblastoma presenting as mechanical neck pain: a case report

    OpenAIRE

    1994-01-01

    Osteoblastoma is a benign bone-forming tumor that represents approximately 1% of all primary bone tumors. It occurs 40% of the time in the spine, most commonly in the posterior elements. The clinical presentation in this case is of chronic neck pain and stiffness. Although most lesions are well visualized on plain films, a bone scan or CT scan may be of better diagnostic value. Treatment is via surgical excision. In this report we present a case of cervical osteoblastoma mistaken for mechanic...

  10. Long-term experience with implanted intrathecal drug administration systems for failed back syndrome and chronic mechanical low back pain

    Directory of Open Access Journals (Sweden)

    Treharne GJ

    2002-06-01

    Full Text Available Abstract Background Continuous intrathecal drug delivery has been shown in open studies to improve pain and quality of life in those with intractable back pain who have had spinal surgery. There is limited data on long term effects and and even less for patients with mechanical back pain without prior spinal surgery. Methods We have investigated spinal drug administration systems for patients with failed back syndrome and chronic mechanical low back pain by patient questionnaire study of the efficacy of this therapy and a case notes review. Results 36 patients (97% of 37 approached completed questionnaires, 24 with failed back syndrome and 12 with chronic mechanical low back pain. Recalled pre-treatment levels with current post-treatment levels of pain and a range of quality of life measures (recorded on 11-point numerical rating scales were compared. Pain improved significantly in both groups (Wilcoxan signed ranks test, p 0.005, Wilcoxan signed ranks test with Bonferroni correction. Diamorphine was used in all 37 patients, bupivacaine in 32, clonidine in 27 and baclofen in 3. The mean dose of diamorphine increased for the first 2 years but did not change 2–6 years post implant, averaging 4.5 mg/day. Revision surgery was required in 24% of cases, but reduced to 12% in the later years of our experience. Conclusions We conclude that spinal drug administration systems appear to be of benefit in alleviating pain in the failed back syndrome and chronic mechanical low back pain but need to be examined prospectively.

  11. General trigeminospinal central sensitization and impaired descending pain inhibitory controls contribute to migraine progression.

    Science.gov (United States)

    Boyer, Nelly; Dallel, Radhouane; Artola, Alain; Monconduit, Lénaïc

    2014-07-01

    Migraine is a chronic disease with episodic manifestations. In a subgroup, attack frequency increases over time, leading to chronic migraine. One of the most important risk factors for migraine progression is frequency of headache attacks at baseline. Unfortunately, the actual effects of repeated activation of dural nociceptors are poorly known. We investigated the behavioral, anatomical, and electrophysiological changes induced by repeated low- and high-intensity stimulation of meningeal nociceptor by injecting an inflammatory soup in rats. Single high-intensity, but not low-intensity, stimulation produces a reversible cephalic allodynia. Upon repetition, however, low-intensity stimulation, too, induces a reversible cephalic allodynia, and high-intensity, reversible cephalic and extracephalic allodynia. Moreover, cephalic allodynia becomes, in part, persistent upon repeated high-intensity stimulation. Fos expression reveals that a single high-intensity stimulation already leads to widespread, trigeminal, and spinal central sensitization, and that such general central sensitization potentiates upon repetition. Trigeminovascular nociceptive neurons become persistently sensitized and their diffuse noxious inhibitory controls (DNIC) concomitantly impaired. Thus, compared with single stimulation, repeated dural nociceptor activation specifically leads to: 1) a gradual worsening of cutaneous hypersensitivity and general neuronal hyperexcitability and 2) spreading of cutaneous hypersensitivity superimposed on 3) persistent cephalic cutaneous hypersensitivity and trigeminal central sensitization. Such repetition-induced development of central sensitization and its consequence, cutaneous allodynia, may arise from both the general neuronal hyperexcitability that results from DNIC impairment and hyperexcitability that likely develops in trigeminal nociceptive neurons in response to their repetitive activation. These neuronal changes may in turn elevate the risk for

  12. Antinociceptive effects of neurotropin in a rat model of central neuropathic pain: DSP-4 induced noradrenergic lesion.

    Science.gov (United States)

    Kudo, Takashi; Kushikata, Tetsuya; Kudo, Mihoko; Kudo, Tsuyoshi; Hirota, Kazuyoshi

    2011-09-26

    Neurotropin is a nonprotein extract isolated from inflamed skin of rabbits inoculated with vaccinia virus, and used for treatment of neuropathic pain. In the present study, we have determined whether neurotropin could exert antinociceptive action using the central neuropathic pain model that we recently established. Rats were randomly allocated to 3 groups: Sham group (n=20), DSP-4 [N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine] group (50mg/kg ip, n=18), and DSP-4+5,7-DHT [5,7-dihydroxytryptamine] group (ip DSP-4 50mg/kg+icv 5,7-DHT 200μg, n=18). In Sham, DSP-4 and DSP-4+5,7-DHT groups, the effects of ip neurotropin (100NU/Kg) on hot-plate latency in rats with no lesion, noradrenergic neuron depletion and both noradrenergic and serotonergic neuronal depletion were studied, respectively. Rats in each group were subdivided equally to 2 subgroups: saline and neurotropin. After completion of the hot-plate tests, each rat was decapitated, the cerebral cortex was dissected from its internal structure for measurement of norepinephrine contents. Hot-plate latency significantly decreased by ∼40% 10 days after ip DSP-4 or after ip DSP-4 and 5,7-DHT. Norepinephrine contents in DSP-4 treated rats (55.6±6.3ng/ng tissue) and DSP-4+5,7-DHT treated rats (35.3±6.3ng/ng tissue) were significantly lower than those in intact rats (131.6±5.7ng/ng tissue, p<0.01). Neurotropin significantly increased the area under the curve (AUC) of the hot-plate latency in the DSP-4 and DSP-4+5,7-DHT groups but not in the Sham group. There was a significant correlation between AUC and norepinephrine contents in saline subgroup (p<0.01, r=0.597) but not in neurotropin subgroup in DSP-4 group. Neurotropin exerted an antinociceptive effect in DSP-4 induced central neuropathic pain. The present data suggest neuronal pathways other than descending inhibitory noradrenergic and serotonergic systems may be involved in neurotropin mediated antinociception.

  13. Delineating inflammatory and mechanical sub-types of low back pain: a pilot survey of fifty low back pain patients in a chiropractic setting

    Directory of Open Access Journals (Sweden)

    Riksman Janine S

    2011-02-01

    Full Text Available Abstract Background An instrument known as the Mechanical and Inflammatory Low Back Pain (MAIL Scale was drafted using the results of a previous expert opinion study. A pilot survey was conducted to test the feasibility of a larger study designed to determine the MAIL Scale's ability to distinguish two potential subgroups of low back pain: inflammatory and mechanical. Methods Patients with a primary complaint of low back pain (LBP presenting to chiropractic clinics in Perth, Western Australia were asked to fill out the MAIL Scale questionnaire. The instrument's ability to separate patients into inflammatory and mechanical subgroups of LBP was examined using the mean score of each notional subgroup as an arbitrary cut-off point. Results Data were collected from 50 patients. The MAIL Scale did not appear to separate cases of LBP into the two notionally distinct groups of inflammatory (n = 6 or mechanical (n = 5. A larger "mixed symptom" group (n = 39 was revealed. Conclusions In this pilot study the MAIL Scale was unable to clearly discriminate between what is thought to be mechanical and inflammatory LBP in 50 cases seen in a chiropractic setting. However, the small sample size means any conclusions must be viewed with caution. Further research within a larger study population may be warranted and feasible.

  14. Central activation of TRPV1 and TRPA1 by novel endogenous agonists contributes to mechanical allodynia and thermal hyperalgesia after burn injury.

    Science.gov (United States)

    Green, Dustin; Ruparel, Shivani; Gao, Xiaoli; Ruparel, Nikita; Patil, Mayur; Akopian, Armen; Hargreaves, Kenneth

    2016-01-01

    The primary complaint of burn victims is an intense, often devastating spontaneous pain, with persistence of mechanical and thermal allodynia. The transient receptor potential channels, TRPV1 and TRPA1, are expressed by a subset of nociceptive sensory neurons and contribute to inflammatory hypersensitivity. Although their function in the periphery is well known, a role for these TRP channels in central pain mechanisms is less well defined. Lipid agonists of TRPV1 are released from peripheral tissues via enzymatic oxidation after burn injury; however, it is not known if burn injury triggers the release of oxidized lipids in the spinal cord. Accordingly, we evaluated whether burn injury evoked the central release of oxidized lipids . Analysis of lipid extracts of spinal cord tissue with HPLC-MS revealed a significant increase in levels of the epoxide and diol metabolites of linoleic acid: 9,10-DiHOME, 12,13-DiHOME, 9(10)-EpOME, and 12(13)-EpOME, that was reduced after intrathecal (i.t.) injection of the oxidative enzyme inhibitor ketoconazole. Moreover, we found that these four lipid metabolites were capable of specifically activating both TRPV1 and TRPA1. Intrathecal injection of specific antagonists to TRPV1 (AMG-517) or TRPA1 (HC-030031) significantly reduced post-burn mechanical and thermal allodynia. Finally, i.t. injection of ketoconazole significantly reversed post-burn mechanical and thermal allodynia. Our data indicate that spinal cord TRPV1 and TRPA1 contributes to pain after burn and identifies a novel class of oxidized lipids elevated in the spinal cord after burn injury. Since the management of burn pain is problematic, these findings point to a novel approach for treating post-burn pain.

  15. [Labor pain from the viewpoint of the modern knowledge of pain physiology].

    Science.gov (United States)

    Frahm, R; Mundt, A

    1986-01-01

    The valuation and treatment of labor pains require complete morphological and anatomical informations about the neuronal systems concerned. A review is given about modern model conceptions in perception, modulation and transmission of pain, based on the latest knowledges in the pain research. The identification of central control- and modulation systems is very important for the actual theory of pain. Pains and also labor pains are caused as a result of complicated nerval connective principles with slim relation to endocrinological system and are also connected with a lot of individual psychical influences. Essentially, four functional stages are passed from the place of nociceptive perception to the registration in the telencephalon. These are depicted in consideration of numerous afferent and efferent, biochemical and hormonal, stimulated and inhibited modulation effects. Various pain inhibitory mechanisms, such as biogenic amines and endogenous opioids are discussed by reference to interesting aspects in new therapeutical possibilities in treatment of pain and also of labor pains.

  16. Population pressure, mechanization, and landlessness in Central Thailand.

    Science.gov (United States)

    Ramsay, A

    1985-04-01

    This paper evaluates 2 explanations of the growing landlessness noted in contemporary Thailand. The 1st conceptualizes landlessness as a natural consequence of population pressures on limited agricultural land, while the 2nd blames technologic changes that give larger farmers substantial advantages over smaller ones. The validity of the 2 explanations is tested by examining differing levels of landlessness among provinces in Thailand's Central Plain. Overall, 14% of farm households in the Central Plain area were landless in 1974-75; however, the range extended from 4% in Kanchanaburi to 38% in Ayuthaya province. Multiple regression analysis suggests a strong association betweeen the percentage of landless agricultural worker families among farm households in the Central Plain and new technology. It is hypothesized that it is not that technology causes landlessness, but that it creates a demand for agricultural labor. As more and more arable land in Thailand becomes occupied, it becomes increasingly difficult for farmers to open new land. Thus, many choose to become an agricultural laborer or to leave agriculture altogether. The commercialization of rice agriculture made it possible to find wage labor in the villages of the Central Plain in the 1930s and played a role in the creation of a landless labor class. Demand factors appear to be of importance in determining which provinces have the highest concentrations of farm workers, but the closing frontier hypothesis seems to explain the origins of landless agricultural workers in Central Plain provinces. A closing frontier is significantly associated with outmigration. Provinces with the least idle land are closest to having a closed frontier.

  17. Cognitive-emotional sensitization contributes to wind-up-like pain in phantom limb pain patients

    DEFF Research Database (Denmark)

    Vase, Lene; Nikolajsen, Lone; Christensen, Bente;

    2011-01-01

    ). Catastrophizing accounted for 35% of the variance in phantom limb pain (p=0.001) independently of anxiety and depression. Catastrophizing was also positively associated with wind-up-like pain in non-medicated patients (p=0.015), but not to pain thresholds. These findings suggest that cognitive-emotional......Peripheral mechanisms are known to play a role in phantom pain following limb amputation, and more recently it has been suggested that central mechanisms may also be of importance. Some patients seem to have a psychological sensitivity that predisposes them to react with pain catastrophizing after...... amputation of a limb, and this coping style may contribute to increased facilitation, impaired modulation of nociceptive signals, or both. To investigate how pain catastrophizing, independently of anxiety and depression, may contribute to phantom limb pain and to alterations in pain processing twenty...

  18. Neuropathic pain

    DEFF Research Database (Denmark)

    Colloca, Luana; Ludman, Taylor; Bouhassira, Didier

    2017-01-01

    Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons, and affects 7-10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing...... to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central...... nervous system all have been implicated in neuropathic pain. The burden of chronic neuropathic pain seems to be related to the complexity of neuropathic symptoms, poor outcomes and difficult treatment decisions. Importantly, quality of life is impaired in patients with neuropathic pain owing to increased...

  19. Cortex glial cells activation, associated with lowered mechanical thresholds and motor dysfunction, persists into adulthood after neonatal pain.

    Science.gov (United States)

    Sanada, Luciana Sayuri; Sato, Karina Laurenti; Machado, Nathalia Leilane Berto; Carmo, Elisabete de Cássia do; Sluka, Kathleen A; Fazan, Valeria Paula Sassoli

    2014-06-01

    We investigated if changes in glial activity in cortical areas that process nociceptive stimuli persisted in adult rats after neonatal injury. Neonatal pain was induced by repetitive needle prickling on the right paw, twice per day for 15 days starting at birth. Wistar rats received either neonatal pain or tactile stimulation and were tested behaviorally for mechanical withdrawal thresholds of the paws and gait alterations, after 15 (P15) or 180 (P180) days of life. Brains from rats on P15 and P180 were immunostained for glial markers (GFAP, MCP-1, OX-42) and the following cortical areas were analyzed for immunoreactivity density: prefrontal, anterior insular, anterior cingulated, somatosensory and motor cortices. Withdrawal thresholds of the stimulated paw remained decreased on P180 after neonatal pain when compared to controls. Neonatal pain animals showed increased density for both GFAP and MCP-1 staining, but not for OX-42, in all investigated cortical areas on both experimental times (P15 and P180). Painful stimuli in the neonatal period produced pain behaviors immediately after injury that persisted in adult life, and was accompanied by increase in the glial markers density in cortical areas that process and interpret pain. Thus, long-lasting changes in cortical glial activity could be, at least in part, responsible for the persistent hyperalgesia in adult rats that suffered from neonatal pain.

  20. Managing Neuropathic Pain in Dogs.

    Science.gov (United States)

    Moore, Sarah A

    2016-01-01

    Disorders of the somatosensory system such as neuropathic pain are common in people with chronic neurologic and musculoskeletal diseases, yet these conditions remain an underappreciated morbidity in veterinary patients. This is likely because assessment of neuropathic pain in people relies heavily on self-reporting, something our veterinary patients are not able to do. The development of neuropathic pain is a complex phenomenon, and concepts related to it are frequently not addressed in the standard veterinary medical curriculum such that veterinarians may not recognize this as a potential problem in patients. The goals of this review are to discuss basic concepts in the pathophysiology of neuropathic pain, provide definitions for common clinical terms used in association with the condition, and discuss pharmacological treatment options for dogs with neuropathic pain. The development of neuropathic pain involves key mechanisms such as ectopic afferent nerve activity, peripheral sensitization, central sensitization, impaired inhibitory modulation, and pathologic activation of microglia. Treatments aimed at reducing neuropathic pain are targeted at one or more of these mechanisms. Several drugs are commonly used in the veterinary clinical setting to treat neuropathic pain. These include gabapentin, pregabalin, amantadine, and amitriptyline. Proposed mechanisms of action for each drug, and known pharmacokinetic profiles in dogs are discussed. Strong evidence exists in the human literature for the utility of most of these treatments, but clinical veterinary-specific literature is currently limited. Future studies should focus on objective methods to document neuropathic pain and monitor response to therapy in veterinary patients.

  1. Persistent postsurgical pain: risk factors and prevention

    DEFF Research Database (Denmark)

    Kehlet, Henrik; Jensen, Troels Staehelin; Woolf, Clifford J.

    2006-01-01

    Acute postoperative pain is followed by persistent pain in 10-50% of individuals after common operations, such as groin hernia repair, breast and thoracic surgery, leg amputation, and coronary artery bypass surgery. Since chronic pain can be severe in about 2-10% of these patients, persistent...... therapy for postoperative pain should be investigated, since the intensity of acute postoperative pain correlates with the risk of developing a persistent pain state. Finally, the role of genetic factors should be studied, since only a proportion of patients with intraoperative nerve damage develop...... chronic pain. Based on information about the molecular mechanisms that affect changes to the peripheral and central nervous system in neuropathic pain, several opportunities exist for multimodal pharmacological intervention. Here, we outline strategies for identification of patients at risk...

  2. Diagnosis and Treatment of Phantom Limb Pain: Mechanisms and Option FLow Sheet.

    Science.gov (United States)

    1982-08-01

    related to causalgia like burning pain.4 u Beta blockers may be of some use to treat this portion of the problem. A recent report shows success upon...psychological aspects. Annals N.Y. Acad. Sci. 74:14, 1958. 4. Marsland, A., Weeks, J., Atkinson, R., and Leong, M.: Phantom limb pain: A case for beta ... blockers ? Pain 12, 295, 1982. 5. Meizack, R.: Phantom limb pain: Implications for treatment of pathologic pain. Anesthesiology 35(4):409, 񓟓. 6

  3. Central Mechanisms of Abnormal Sympathoexcitation in Chronic Heart Failure

    Directory of Open Access Journals (Sweden)

    Takuya Kishi

    2012-01-01

    Full Text Available It has been recognized that the sympathetic nervous system is abnormally activated in chronic heart failure, and leads to further worsening chronic heart failure. In the treatment of chronic heart failure many clinical studies have already suggested that the inhibition of the abnormal sympathetic hyperactivity by beta blockers is beneficial. It has been classically considered that abnormal sympathetic hyperactivity in chronic heart failure is caused by the enhancement of excitatory inputs including changes in peripheral baroreceptor and chemoreceptor reflexes and chemical mediators that control sympathetic outflow. Recently, the abnormalities in the central regulation of sympathetic nerve activity mediated by brain renin angiotensin system-oxidative stress axis and/or proinflammatory cytokines have been focused. Central renin angiotensin system, proinflammatory cytokines, and the interaction between them have been determined as the target of the sympathoinhibitory treatment in experimental animal models with chronic heart failure. In conclusion, we must recognize that chronic heart failure is a syndrome with an abnormal sympathoexcitation, which is caused by the abnormalities in the central regulation of sympathetic nerve activity.

  4. [Pain and fear in animals].

    Science.gov (United States)

    Loeffler, K

    1993-02-01

    Pain and fear are feelings of reluctance, which result in a behaviour of avoidance. They are protective mechanisms and are only partly approachable to the quantification with natural scientific methods. It will pointed to the central role of the diencephalon, limbic system and the cerebral cortex concerning the processing and valuation of mental state. The recognition of clinical symptoms and precise behavioural observations are an essential aid to assess the state of pain and fear in animals.

  5. Central and peripheral mechanisms by which ghrelin regulates gut motility.

    Science.gov (United States)

    Peeters, T L

    2003-12-01

    Ghrelin is the recently discovered endogenous ligand for the growth hormone secretagogue receptor. This receptor had previously been characterized based on the stimulatory effect of synthetic peptides, enkephalin analogues, on growth hormone secretion by pituitary somatotrophs. Surprisingly, ghrelin is most abundant in the stomach, suggesting that it may have effects beyond the stimulation of growth hormone in the pituitary and that it is a new brain-gut peptide. There is now increasing evidence that ghrelin stimulates motor activity in the gastrointestinal tract. Thus ghrelin induces the migrating motor complex and accelerates gastric emptying. These are effects typical for motilin, the only peptide structurally related to ghrelin. Moreover, the receptors of both peptides are structurally related as well. The motor effects of ghrelin require rather high concentrations, while motilin at high concentrations stimulates growth hormone release. These data suggest cross-reactivity. However, in vitro binding and contractility studies in the rabbit, the classical model to study motilin agonists, show that ghrelin has very weak if any interaction with the motilin receptor. Similarly, in cell lines expressing the receptors for both peptides there is no evidence for cross-reactivity. This corresponds to the fact that the pharmacophore of both peptides is quite different. Therefore, the motor effects must be due to the stimulation of specific central or peripheral ghrelin receptors. In the guinea pig there is evidence from electrophysiology, immunohistochemistry and calcium imaging studies for ghrelin receptors on myenteric neurons. This provides the morphological basis for peripheral effects of ghrelin. In rats, ghrelin, but not motilin, enhances the response of muscle strips to electrical field stimulation by activating cholinergic pathways. In rabbits the opposite is true but some synthetic ghrelin agonists have weak effects which cannot be blocked by motilin antagonists

  6. Do subjects with whiplash-associated disorders respond differently in the short-term to manual therapy and exercise than those with mechanical neck pain?

    DEFF Research Database (Denmark)

    Castaldo, Matteo; Catena, Antonella; Chiarotto, Alessandro

    2017-01-01

    with whiplash-associated disorders participated. Clinical and physical outcomes including neck pain intensity, neck-related disability, and pain area, as well as cervical range of motion and pressure pain thresholds over the upper trapezius and tibialis anterior muscles, were obtained at baseline and after...... outcomes and cervical range of motion with both groups experiencing similar improvements (all P  0.222). CONCLUSIONS : The current clinical trial found that subjects with mechanical neck pain and whiplash......OBJECTIVE : To compare the short-term effects of manual therapy and exercise on pain, related disability, range of motion, and pressure pain thresholds between subjects with mechanical neck pain and whiplash-associated disorders. METHODS : Twenty-two subjects with mechanical neck pain and 28...

  7. La estimulación eléctrica de la corteza motora para el tratamiento del dolor central y dolor periférico por desaferentización Electrical stimulation of the motor cortex for the management of central pain and peripheral pain caused by desafferentiation

    Directory of Open Access Journals (Sweden)

    J. V. Pesudo

    2004-09-01

    published on the matter. Currently, its major indications are central pain, mainly thalamic, and trigeminal pain caused by desafferentation. The response to barbiturates without response to opiates, the relative preservation of motor and sensitive pathways and the response to transcranial magnetic stimulation predict a good result. Several methods are used to determine the area that has to be stimulated: SSEP, intraoperatory stimulation, neuronavegation, functional MRI. The stimulation parameters recommended vary according to the author. Its mechanism of action is still not well understood, but the most accepted theories are the activation of areas that modulate pain and the inhibition of the transmission of nociceptive stimuli at the medullar level.

  8. A STUDY TO EXPLORE PREFERRED METHOD OF TREATMENT AMONG PHYSIOTHERAPISTS FOR MECHANICAL LOW BACK PAIN

    Directory of Open Access Journals (Sweden)

    Iram Iqbal Shamsi

    2016-02-01

    Full Text Available Background: Conservative treatment remains the standard of care for treating nonspecific mechanical low back pain which is very common problem all around the world. In Pakistan, physiotherapists encounter this problem frequently in clinical practice. Despite a wide variety of treatments, 100 percent results have been unachievable. The purpose of this study was to establish a Standard and Uniform Physiotherapy Protocol for mechanical low back pain. Methods: To achieve the objective of this study, a questionnaire with structured and open ended questions were designed and distributed to hospitals and private clinics. 139 questionnaires were distributed from 1st March 2009 to 30th May 2009. By the end of July 5, 2009, 101 were filled and returned. The data was analyzed using descriptive statistics. Results: Results have shown that McKenzie (25%, combination of McKenzie and Maitland (9% were among the preferred techniques. However, 14% did not use a specific technique. The preferred physical agents were hot packs (22%, combination of hot packs, ultrasound, TENS (22%. However, 4% did not prefer any physical agent. Out of 101 subjects per week, 20 subjects were treated for 7 days, 11 were treated for 5 days, 53 were treated for 3 days, 6 were treated for 2 days and 11 were treated for 1 day. The recurrence rate was 32.14% for those who were treated for six days, 34.75% for those treated for 5 days, 33.55% for those who were treated for 3 days, 31.25% for those who were treated for 2 days, and 37.55% for those who were treated for one day. 39% did not consider ergonomical issues while 27% did not advice regarding the patient nutritional facts. Average depression among patients was 24.7%. Conclusion: This study shows that the results for mechanical low back pain were not as effective with combination of techniques and modalities. If the physiotherapists had taken the psychological factors, ergonomical approach and nutrition into consideration, the

  9. 中枢性卒中后疼痛的诊断评价和治疗%Diagnostic evaluation and treatment of central poststroke pain

    Institute of Scientific and Technical Information of China (English)

    王学平; 李建辉; 米海娟

    2016-01-01

    Central poststroke pain (CPSP) is a neuropathic pain syndrome that can occur after stroke.This syndrome is characterized by pain and sensory abnormalities in the body parts that correspond to the stroke lesion.CPSP occurs ia 1%-12% of stroke patients.A definite diagnosis of CPSP is difficult,mainly because of the variable clinical picture,the frequent concurrence of several pain types,and the lack of clear diagnostic criteria for CPSP.Management of the CPSP is challenging.This article reviews the diagnostic evaluation and treatment of CPSP.%中枢性卒中后疼痛(central poststroke pain,CPSP)是卒中后发生的一种神经性疼痛综合征,以与卒中病损相对应的躯体部位疼痛或感觉异常为特征.CPSP在卒中患者中的发生率为1%~12%.确诊CPSP比较困难,主要是由于临床表现的不确定性、常与多种类型的疼痛同时发生以及缺乏明确的诊断标准.CPSP的治疗亦具有挑战性.文章对CPSP的诊断评价和治疗进行了综述.

  10. Muscle function and origin of pain in fibromyalgia

    DEFF Research Database (Denmark)

    Bennett, R M; Jacobsen, Søren

    1994-01-01

    It may be concluded that both peripheral and central mechanisms may operate in the pathophysiology of both impaired muscle function and pain in FM. These mechanisms may in part be attributable to physical deconditioning and disuse of muscle secondary to the characteristic pain and fatigue so ofte...

  11. 骨癌性疼痛病理机制%The mechanism of bone cancer pain

    Institute of Scientific and Technical Information of China (English)

    俞芳; 王祥瑞

    2013-01-01

    Background Bone Cancer Pain (BCP) or Cancer-Induced Bone Pain is the most common symptom of bone tumors,affecting up to 85% of the patients with primary bone cancer or secondary metastases,causing a significant decrease in the quality of life of patients with more advanced stages of cancer with pain associated anxiety,depression and loss of functions.So far,BCP has proven to be a challenge to manage clinically.However,with the recent development of animal models demonstrating pathological mechanisms of BCP,researchers hope to gain insights into possible manage methods in the future.Objective osummarize the pathological mechanisms of BCP,which maight offer new ideas or directions for its management.Content This article will give a detailed summary of the pathological mechanisms related to BCP by reviewing research articles published in last 5 years.Trend The current trend in research has been focusing on the developing treatments based on the complicated pathological mechanisms of BCP,which mostly involves structural,physiological and pharmacological alterations.Unclear because traitements based on the pathological mechanisms might be beneficial in the management of BCP.%背景 骨癌性疼痛(bone cancer pain,BCP)或癌性骨痛是原发性恶性骨肿瘤或者骨转移癌患者最主要的临床问题,约85%的骨恶性肿瘤患者出现疼痛,从而导致焦虑甚至抑郁,降低其终末期的生活质量.BCP目前临床上难以达到彻底的疼痛缓解.近些年来,随着BCP动物模型的建立和成熟,其病理生理机制正逐渐被人阐述. 目的 总结BCP涉及到的病理机制,希望对临床寻找基于病理机制的治疗提供新的思路. 内容 综合和总结近5年内的研究文章,阐述BCP涉及的病理机制. 趋向 BCP病理机制复杂,涉及到肿瘤-脊髓.大脑的结构性、生理性、药理性等以及细胞因子和通路等的改变,研究建立在机制研究基础上的治疗手段将会给患者带来福音.

  12. Treatment of neuropathic pain: a new method, transdermic route

    Directory of Open Access Journals (Sweden)

    Vittorio Iorno

    2006-05-01

    Full Text Available The therapy of neuropathic pain is difficult due to the lack of reliable classification. This pain can be defined as peripheral, central, mixed or based on the underlying mechanisms. Following this last criterium, we selected 44 patients affected by peripheral neuropathic pain. The not invasive care consisted in giving a pharmacological cocktail by a transdermal hydroelectrophoretic technique. 34% of all patients showed a pain relief between 70 and 99% (good results, while 9% had a complete resolution of pain (very good results. We concluded suggesting the transdermic hydroelectrophoretic techniques as useful and efficient in drugs administration to patients with peripheral neuropathic pain.

  13. Cerebral decreases in opioid receptor binding in patients with central neuropathic pain measured by [11C]diprenorphine binding and PET.

    Science.gov (United States)

    Jones, Anthony K P; Watabe, Hiroshi; Cunningham, Vin J; Jones, Terry

    2004-10-01

    Central neuropathic pain (CNP) is pain resulting from damage to the central nervous system. Up till now, it has not been possible to identify a common lesion or pharmacological deficit in these patients. This preliminary study in a group of patients with CNP with predominantly post-stroke pain, demonstrates that there is significantly less opioid receptor binding in a number of cortical and sub-cortical structures that are mostly, but not exclusively, within the medial pain system in patients compared to age-matched pain-free controls. The reductions in opioid receptor binding within the medial system were observed mainly in the dorsolateral (Brodman area 10) and anterior cingulate (Brodman area 24 with some extension into area 23) and insula cortices and the thalamus. There were also reductions in the lateral pain system within the inferior parietal cortex (Brodman area 40). These changes in binding could not be accounted for by the cerebral lesions shown by CT or MRI, which were outside the areas of reduced binding and the human pain system. To our knowledge this is the first systematic demonstration of a reduction in opioid receptor-binding capacity in neurones within the human nociceptive system in patients with CNP. This may be a key common factor resulting in undamped nociceptor activity within some of the structures that are predominantly within the medial nociceptive system. If confirmed, these findings may explain why certain patients with CNP require high doses of synthetic opiates to achieve optimum analgesia. The findings also raise the possibility of new pharmacological approaches to treatment.

  14. Pain mechanisms and ultrasonic inflammatory activity as prognostic factors in patients with psoriatic arthritis

    DEFF Research Database (Denmark)

    Højgaard, Pil; Christensen, Robin; Dreyer, Lene;

    2016-01-01

    )) will be prospectively recruited from outpatient clinics in Copenhagen. All data (demographics, clinical, imaging, blood samples and patient-reported outcomes) will be collected at baseline and after 4 months. Pain is assessed by the PainDETECT Questionnaire, Visual Analogue Scale for pain, Swollen to Tender Joint Count...

  15. Approaches to treating pain in terms of the mechanisms of its development

    Directory of Open Access Journals (Sweden)

    Galina Rashidovna Imametdinova

    2013-03-01

    Full Text Available The paper considers problems in the treatment of acute and chronic pain in patients with rheumatic diseases and shows the role of inflammation and muscle spasm in the pathogenesis of acute and chronic pain. It gives the results of clinical trials and the clinical use of nimesulide (Nise ® and tizanidine (Sirdalud ® in the treatment of acute and chronic pain.

  16. Approaches to treating pain in terms of the mechanisms of its development

    Directory of Open Access Journals (Sweden)

    Galina Rashidovna Imametdinova

    2013-01-01

    Full Text Available The paper considers problems in the treatment of acute and chronic pain in patients with rheumatic diseases and shows the role of inflammation and muscle spasm in the pathogenesis of acute and chronic pain. It gives the results of clinical trials and the clinical use of nimesulide (Nise ® and tizanidine (Sirdalud ® in the treatment of acute and chronic pain.

  17. Yokukansan Improves Mechanical Allodynia through the Regulation of Interleukin-6 Expression in the Spinal Cord in Mice with Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Shigeru Ebisawa

    2015-01-01

    Full Text Available Neuropathic pain is caused by nerve injury. Yokukansan (Yi-Gan San, a traditional Japanese (Kampo medicine, has been widely used for neuropathic pain control. However, the analgesic mechanisms remain unknown. In this study, we investigated the analgesic mechanisms of yokukansan in a mouse model of neuropathic pain. Partial sciatic nerve ligation (PSL induced mechanical allodynia in mice. Repetitive oral administration of the extracts of yokukansan and the constituent herbal medicine Atractylodis Lanceae Rhizoma, but not Glycyrrhizae Radix, relieved mechanical allodynia in the PSL mice and inhibited the PSL-induced expression of interleukin- (IL- 6 mRNA in the spinal cord. Yokukansan did not attenuate intrathecal IL-6-induced mechanical allodynia. IL-6 immunoreactivity was detected in microglia and astrocytes in the spinal dorsal horn. These results suggest that yokukansan relieves mechanical allodynia in PSL mice by regulating the expression of IL-6 in astrocytes and/or microglia in the spinal cord. In addition, the components of Atractylodis Lanceae Rhizoma, one of the constituent herbal medicines in yokukansan, may play an important role in the regulation of IL-6 expression and neuropathic pain control.

  18. Sensory stimulation (TENS): effects of parameter manipulation on mechanical pain thresholds in healthy human subjects.

    Science.gov (United States)

    Chesterton, Linda S; Barlas, Panos; Foster, Nadine E; Lundeberg, Thomas; Wright, Christine C; Baxter, G David

    2002-09-01

    Transcutaneous electrical nerve stimulation (TENS) is a popular form of electrostimulation. Despite an extensive research base, there remains no consensus regarding the parameter selection required to achieve maximal hypoalgesic effects. The aim of this double blind, sham-controlled study was to investigate the relative hypoalgesic effects of different TENS parameters (frequency, intensity and stimulation site) upon experimentally induced mechanical pain. Two hundred and forty participants were recruited in order to provide statistical analysis with 80% power at alpha = 0.05. Subjects were randomised to one of the six TENS groups, a control, and a sham TENS group (n = 30, 15 males, 15 females, per group). TENS groups differed in their combinations of stimulation; frequency (4 or 110 Hz), intensity ('to tolerance' or 'strong but comfortable') and stimulation site (segmental--over the distribution of the radial nerve or, extrasegmental--over acupuncture point 'gall bladder 34', or a combination of both segmental and extrasegmental). Pulse duration was fixed at 200 micros. Stimulation was delivered for 30 min and subjects were then monitored for a further 30 min. Mechanical pain threshold (MPT) was measured using a pressure algometer and taken from the first dorsal interosseous muscle of the dominant hand, ipsilateral to the stimulation site. MPT measures were taken, at baseline, and at 10-min intervals for 60 min. Difference scores were analysed using repeated measures and one-way ANOVA and relevant post hoc tests. Low frequency, high intensity, extrasegmental stimulation produced a rapid onset hypoalgesic effect, which increased during the stimulation period (P < 0.0005 control and sham) and was sustained for 30 min post-stimulation (P < 0.0005(control), P = 0.024(sham)). Whilst high frequency, 'strong but comfortable' intensity, segmental stimulation produced comparable hypoalgesic levels during stimulation, this effect was not sustained post

  19. Are There Abnormalities in Peripheral and Central Components of Somatosensory Evoked Potentials in Non-Specific Chronic Low Back Pain?

    Science.gov (United States)

    Puta, Christian; Franz, Marcel; Blume, Kathrin R.; Gabriel, Holger H. W.; Miltner, Wolfgang H. R.; Weiss, Thomas

    2016-01-01

    Chronic low back pain (CLBP) was shown to be associated with longer reflex response latencies of trunk muscles during external upper limb perturbations. One theoretical, but rarely investigated possibility for longer reflex latencies might be related to modulated somatosensory information processing. Therefore, the present study investigated somatosensory evoked potentials (SEPs) to median nerve stimulation in CLBP patients and healthy controls (HC). Latencies of the peripheral N9 SEP component were used as the primary outcome. In addition, latencies and amplitudes of the central N20 SEP component, sensory thresholds, motor thresholds and nerve conduction velocity were also analyzed in CLBP patients and HC. There is a trend for the CLBP patients to exhibit longer N9 latencies at the ipsilateral Erb’s point compared to HC. This trend is substantiated by significantly longer N9 latencies in CLBP patients compared to normative data. None of the other parameters showed any significant difference between CLBP patients and HC. Overall, our data indicate small differences of the peripheral N9 SEP component; however, these differences cannot explain the reflex delay observed in CLBP patients. While it was important to rule out the contribution of early somatosensory processing and to elucidate its contribution to the delayed reflex responses in CLBP patients, further research is needed to find the primary source(s) of time-delayed reflexes in CLBP. PMID:27799904

  20. Alcohol-induced headaches: Evidence for a central mechanism?

    Directory of Open Access Journals (Sweden)

    Alessandro Panconesi

    2016-01-01

    Full Text Available Alcoholic drinks (ADs have been reported as a migraine trigger in about one-third of the migraine patients in retrospective studies. Some studies found that ADs trigger also other primary headaches. The studies concerning the role of ADs in triggering various types of primary headaches published after the International Headache Society classification criteria of 1988 were reviewed, and the pathophysiological mechanisms were discussed. Many studies show that ADs are a trigger of migraine without aura (MO, migraine with aura (MA, cluster headache (CH, and tension-type headache (TH. While data on MO and CH are well delineated, those in MA and TH are discordant. There are sparse reports that ADs are also triggers of less frequent types of primary headache such as familial hemiplegic migraine, hemicrania continua, and paroxysmal hemicrania. However, in some countries, the occurrence of alcohol as headache trigger is negligible, perhaps determined by alcohol habits. The frequency estimates vary widely based on the study approach and population. In fact, prospective studies report a limited importance of ADs as migraine trigger. If ADs are capable of triggering practically all primary headaches, they should act at a common pathogenetic level. The mechanisms of alcohol-provoking headache were discussed in relationship to the principal pathogenetic theories of primary headaches. The conclusion was that vasodilatation is hardly compatible with ADs trigger activity of all primary headaches and a common pathogenetic mechanism at cortical, or more likely at subcortical/brainstem, level is more plausible.

  1. Alcohol-induced headaches: Evidence for a central mechanism?

    Science.gov (United States)

    Panconesi, Alessandro

    2016-01-01

    Alcoholic drinks (ADs) have been reported as a migraine trigger in about one-third of the migraine patients in retrospective studies. Some studies found that ADs trigger also other primary headaches. The studies concerning the role of ADs in triggering various types of primary headaches published after the International Headache Society classification criteria of 1988 were reviewed, and the pathophysiological mechanisms were discussed. Many studies show that ADs are a trigger of migraine without aura (MO), migraine with aura (MA), cluster headache (CH), and tension-type headache (TH). While data on MO and CH are well delineated, those in MA and TH are discordant. There are sparse reports that ADs are also triggers of less frequent types of primary headache such as familial hemiplegic migraine, hemicrania continua, and paroxysmal hemicrania. However, in some countries, the occurrence of alcohol as headache trigger is negligible, perhaps determined by alcohol habits. The frequency estimates vary widely based on the study approach and population. In fact, prospective studies report a limited importance of ADs as migraine trigger. If ADs are capable of triggering practically all primary headaches, they should act at a common pathogenetic level. The mechanisms of alcohol-provoking headache were discussed in relationship to the principal pathogenetic theories of primary headaches. The conclusion was that vasodilatation is hardly compatible with ADs trigger activity of all primary headaches and a common pathogenetic mechanism at cortical, or more likely at subcortical/brainstem, level is more plausible.

  2. Palmitoylethanolamide Is a Disease-Modifying Agent in Peripheral Neuropathy: Pain Relief and Neuroprotection Share a PPAR-Alpha-Mediated Mechanism

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    L. Di Cesare Mannelli

    2013-01-01

    Full Text Available Neuropathic syndromes which are evoked by lesions to the peripheral or central nervous system are extremely difficult to treat, and available drugs rarely joint an antihyperalgesic with a neurorestorative effect. N-Palmitoylethanolamine (PEA exerts antinociceptive effects in several animal models and inhibits peripheral inflammation in rodents. Aimed to evaluate the antineuropathic properties of PEA, a damage of the sciatic nerve was induced in mice by chronic constriction injury (CCI and a subcutaneous daily treatment with 30 mg kg−1 PEA was performed. On the day 14, PEA prevented pain threshold alterations. Histological studies highlighted that CCI induced oedema and an important infiltrate of CD86 positive cells in the sciatic nerve. Moreover, osmicated preparations revealed a decrease in axon diameter and myelin thickness. Repeated treatments with PEA reduced the presence of oedema and macrophage infiltrate, and a significant higher myelin sheath, axonal diameter, and a number of fibers were observable. In PPAR-α null mice PEA treatment failed to induce pain relief as well as to rescue the peripheral nerve from inflammation and structural derangement. These results strongly suggest that PEA, via a PPAR-α-mediated mechanism, can directly intervene in the nervous tissue alterations responsible for pain, starting to prevent macrophage infiltration.

  3. Exploration of conditioned pain modulation effect on long-term potentiation-like pain amplification in humans

    DEFF Research Database (Denmark)

    Xia, Weiwei; Mørch, Carsten Dahl; Matre, D.;

    2017-01-01

    BACKGROUND: This study aimed to explore conditioned pain modulation (CPM) effect on long-term potentiation (LTP)-like pain amplification induced by cutaneous 10-Hz conditioning electrical stimulation (CES). METHODS: Conditioned pain modulation was induced by cold pressor conditioning stimulus (CPCS...... session. Moreover, CPCS resulted in lower pain intensity ratings during CES process but without affecting the SF-MPQ scores between two sessions. The SBF and ST increased after CES and then gradually declined but without differences between CPCS and control sessions. CPM did not affect HPT and pain......). SIGNIFICANCE: Conditioned pain modulation (CPM) may play a role in inhibiting the pain amplificatory process at the central nervous system and prompting central desensitization. CPM has a special inhibition effect for the development of perception amplification to non-painful mechanical stimuli....

  4. Mechanisms of low back pain: a guide for diagnosis and therapy [version 2; referees: 3 approved

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    Massimo Allegri

    2016-10-01

    Full Text Available Chronic low back pain (CLBP is a chronic pain syndrome in the lower back region, lasting for at least 3 months. CLBP represents the second leading cause of disability worldwide being a major welfare and economic problem. The prevalence of CLBP in adults has increased more than 100% in the last decade and continues to increase dramatically in the aging population, affecting both men and women in all ethnic groups, with a significant impact on functional capacity and occupational activities. It can also be influenced by psychological factors, such as stress, depression and/or anxiety. Given this complexity, the diagnostic evaluation of patients with CLBP can be very challenging and requires complex clinical decision-making. Answering the question “what is the pain generator” among the several structures potentially involved in CLBP is a key factor in the management of these patients, since a mis-diagnosis can generate therapeutical mistakes. Traditionally, the notion that the etiology of 80% to 90% of LBP cases is unknown has been mistaken perpetuated across decades. In most cases, low back pain can be attributed to specific pain generator, with its own characteristics and with different therapeutical opportunity. Here we discuss about radicular pain, facet Joint pain, sacro-iliac pain, pain related to lumbar stenosis, discogenic pain. Our article aims to offer to the clinicians a simple guidance to identify pain generators in a safer and faster way, relying a correct diagnosis and further therapeutical approach.

  5. Basolateral amygdala lesion inhibits the development of pain chronicity in neuropathic pain rats.

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    Zheng Li

    Full Text Available BACKGROUND: Chronicity of pain is one of the most interesting questions in chronic pain study. Clinical and experimental data suggest that supraspinal areas responsible for negative emotions such as depression and anxiety contribute to the chronicity of pain. The amygdala is suspected to be a potential structure for the pain chronicity due to its critical role in processing negative emotions and pain information. OBJECTIVE: This study aimed to investigate whether amygdala or its subregions, the basolateral amygdala (BLA and the central medial amygdala (CeA, contributes to the pain chronicity in the spared nerve injury (SNI-induced neuropathic pain model of rats. METHODOLOGY/PRINCIPAL FINDINGS: (1 Before the establishment of the SNI-induced neuropathic pain model of rats, lesion of the amygdaloid complex with stereotaxic injection of ibotenic acid (IBO alleviated mechanical allodynia significantly at days 7 and 14, even no mechanical allodynia at day 28 after SNI; Lesion of the BLA, but not the CeA had similar effects; (2 however, 7 days after SNI when the neuropathic pain model was established, lesion of the amygdala complex or the BLA or the CeA, mechanical allodynia was not affected. CONCLUSION: These results suggest that BLA activities in the early stage after nerve injury might be crucial to the development of pain chronicity, and amygdala-related negative emotions and pain-related memories could promote pain chronicity.

  6. TNFα secretion of monocytes exposed to pulsed radiofrequency treatment: a possible working mechanism of PRF chronic pain management.

    Science.gov (United States)

    Maretto, Fabio; Vennik, Marco; Albers, Kim I; van Duijn, Bert

    2014-06-01

    Pulsed radiofrequency treatment (PRF) is a promising new technique increasingly used in treatment of chronic pain. The molecular working mechanism of PRF is not exactly known and is currently being investigated. This study investigates a possible role of PRF-induced modulation of TNFα secretion by differentiated monocytes in chronic pain management. The results show no significant PRF-induced change in TNFα secretion of lipopolysaccharides (LPS)-stimulated monocytes. However, PRF does significantly increase TNFα secretion of differentiated monocytes that have not been stimulated with LPS. This may indicate a possible role of PRF treatment in increasing TNFα production of nonstimulated monocytes. More research is needed to determine whether this is truly a part of the working mechanism of PRF in chronic pain management and which other factors are involved.

  7. Management of chronic visceral pain.

    Science.gov (United States)

    Olesen, Anne E; Farmer, Adam D; Olesen, Søren S; Aziz, Qasim; Drewes, Asbjørn M

    2016-10-01

    Despite marked differences in underlying pathophysiology, the current management of visceral pain largely follows the guidelines derived from the somatic pain literature. The effective management of patients with chronic visceral pain should be multifaceted, including both pharmacological and psychological interventions, thereby providing a mechanism-orientated approach to treatment. Patients can frequently become disenfranchised, and subsequently disengaged, with healthcare providers leading to repeated consultations. Thus, a key aspect of management is to break this cycle by validating patients' symptoms, adopting an empathic approach and taking time to educate patients. To optimize treatment and outcomes in chronic visceral pain we need to move away from approaches exclusively based on dealing with peripheral nociceptive input toward more holistic strategies, taking into account alterations in central pain processing.

  8. Concepts and mechanisms of generalized central nervous system arousal.

    Science.gov (United States)

    Pfaff, Donald; Ribeiro, Ana; Matthews, James; Kow, Lee-Ming

    2008-01-01

    A concept of generalized arousal of the CNS is presented and given an operational definition that leads to quantitative physical measures. Because this primitive arousal function underlies all motivated behavioral responses, cognitive functions, and emotional expression, disorders of generalized arousal can be associated with a large number of problems in medicine and public health, including vegetative states, attentional disorders, depression, occupational hazards, and problems with sleep and anesthesia. Some of its known mechanisms are briefly reviewed, at the levels of neuroanatomy, neurophysiology, and functional genomics. Generalized arousal contributes to the excitement and the activation of behaviors during specific arousal states. Data are summarized for four genomic/neurochemical systems through which changes in generalized arousal could affect sexual arousal, two of which heighten, and the other two of which reduce arousal.

  9. Altered Pain Sensitivity in Elderly Women with Chronic Neck Pain

    OpenAIRE

    2015-01-01

    Background Age-related changes occur in both the peripheral and central nervous system, yet little is known about the influence of chronic pain on pain sensitivity in older persons. The aim of this study was to investigate pain sensitivity in elders with chronic neck pain compared to healthy elders. Methods Thirty elderly women with chronic neck pain and 30 controls were recruited. Measures of pain sensitivity included pressure pain thresholds, heat/cold pain thresholds and suprathreshold hea...

  10. Mechanical pain sensitivity of deep tissues in children - possible development of myofascial trigger points in children

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    Han Ting-I

    2012-02-01

    Full Text Available Abstract Background It is still unclear when latent myofascial trigger points (MTrPs develop during early life. This study is designed to investigate the mechanical pain sensitivity of deep tissues in children in order to see the possible timing of the development of latent MTrPs and attachment trigger points (A-TrPs in school children. Methods Five hundreds and five healthy school children (age 4- 11 years were investigated. A pressure algometer was used to measure the pressure pain threshold (PPT at three different sites in the brachioradialis muscle: the lateral epicondyle at elbow (site A, assumed to be the A-TrP site, the mid-point of the muscle belly (site B, assumed to be the MTrP site, and the muscle-tendon junction as a control site (site C. Results The results showed that, for all children in this study, the mean PPT values was significantly lower (p p Conclusions It is concluded that a child had increased sensitivity at the tendon attachment site and the muscle belly (endplate zone after age of 4 years. Therefore, it is likely that a child may develop an A-Trp and a latent MTrP at the brachioradialis muscle after the age of 4 years. The changes in sensitivity, or the development for these trigger points, may not be related to the activity level of children aged 7-11 years. Further investigation is still required to indentify the exact timing of the initial occurrence of a-Trps and latent MTrPs.

  11. The Neurobiology of Orofacial Pain and Sleep and Their Interactions.

    Science.gov (United States)

    Lavigne, G J; Sessle, B J

    2016-09-01

    This article provides an overview of the neurobiology of orofacial pain as well as the neural processes underlying sleep, with a particular focus on the mechanisms that underlie pain and sleep interactions including sleep disorders. Acute pain is part of a hypervigilance system that alerts the individual to injury or potential injury of tissues. It can also disturb sleep. Disrupted sleep is often associated with chronic pain states, including those that occur in the orofacial region. The article presents many insights that have been gained in the last few decades into the peripheral and central mechanisms involved in orofacial pain and its modulation, as well as the circuits and processes in the central nervous system that underlie sleep. Although it has become clear that sleep is essential to preserve and maintain health, it has also been found that pain, particularly chronic pain, is commonly associated with disturbed sleep. In the presence of chronic pain, a circular relationship may prevail, with mutual deleterious influences causing an increase in pain and a disruption of sleep. This article also reviews findings that indicate that reducing orofacial pain and improving sleep need to be targeted together in the management of acute to chronic orofacial pain states in order to improve an orofacial pain patient's quality of life, to prevent mood alterations or exacerbation of sleep disorder (e.g., insomnia, sleep-disordered breathing) that can negatively affect their pain, and to promote healing and optimize their health.

  12. The Evaluation of Satisfaction Level of Stability Training Exercises in the Patients with Mechanical Nonspecific Chronic Low Back Pain

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    N. Karimi

    2009-07-01

    Full Text Available Introduction & Objective: There is limited evidence on chronic low back patients' perception and satisfaction of the treatment with spinal stabilization exercises and their overall experience of the treatment program. The objective of this study was to evaluate the satisfaction level of patients with mechanical nonspecific chronic low back pain after participating in a stability training program. Materials & Methods: At first, a methodological study was designed to develop a satisfaction questionnaire, and then content validity and test-retest reliability of it were determined. All patients (n=43 participated in a stability training program within a randomized controlled trial. Finally they filled in satisfaction questionnaire. Results: Distribution of demographic variables were normal (P>0.43. 53.5% of the patients had solitary type occupations. 58.1% had history of sport activities. Also, pain location and extension in 46.5% and 65.2% were in lumbar region only. After stability training program, pain decreased (p<0.001 and functional ability as Oswestry and Quebec scales scores increased (p<0.002 significantly. Overall score of satisfaction questionnaire was 16±4.07.Conclusion: Patients with chronic mechanical low back pain were satisfied after participation in stability training program. Pain reduction and better functional ability may be two factors contributing to the satisfaction of these patients.

  13. Mental Health Comorbidities in Pediatric Chronic Pain: A Narrative Review of Epidemiology, Models, Neurobiological Mechanisms and Treatment

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    Jillian Vinall

    2016-12-01

    Full Text Available Chronic pain during childhood and adolescence can lead to persistent pain problems and mental health disorders into adulthood. Posttraumatic stress disorders and depressive and anxiety disorders are mental health conditions that co-occur at high rates in both adolescent and adult samples, and are linked to heightened impairment and disability. Comorbid chronic pain and psychopathology has been explained by the presence of shared neurobiology and mutually maintaining cognitive-affective and behavioral factors that lead to the development and/or maintenance of both conditions. Particularly within the pediatric chronic pain population, these factors are embedded within the broader context of the parent–child relationship. In this review, we will explore the epidemiology of, and current working models explaining, these comorbidities. Particular emphasis will be made on shared neurobiological mechanisms, given that the majority of previous research to date has centered on cognitive, affective, and behavioral mechanisms. Parental contributions to co-occurring chronic pain and psychopathology in childhood and adolescence will be discussed. Moreover, we will review current treatment recommendations and future directions for both research and practice. We argue that the integration of biological and behavioral approaches will be critical to sufficiently address why these comorbidities exist and how they can best be targeted in treatment.

  14. Mental Health Comorbidities in Pediatric Chronic Pain: A Narrative Review of Epidemiology, Models, Neurobiological Mechanisms and Treatment.

    Science.gov (United States)

    Vinall, Jillian; Pavlova, Maria; Asmundson, Gordon J G; Rasic, Nivez; Noel, Melanie

    2016-12-02

    Chronic pain during childhood and adolescence can lead to persistent pain problems and mental health disorders into adulthood. Posttraumatic stress disorders and depressive and anxiety disorders are mental health conditions that co-occur at high rates in both adolescent and adult samples, and are linked to heightened impairment and disability. Comorbid chronic pain and psychopathology has been explained by the presence of shared neurobiology and mutually maintaining cognitive-affective and behavioral factors that lead to the development and/or maintenance of both conditions. Particularly within the pediatric chronic pain population, these factors are embedded within the broader context of the parent-child relationship. In this review, we will explore the epidemiology of, and current working models explaining, these comorbidities. Particular emphasis will be made on shared neurobiological mechanisms, given that the majority of previous research to date has centered on cognitive, affective, and behavioral mechanisms. Parental contributions to co-occurring chronic pain and psychopathology in childhood and adolescence will be discussed. Moreover, we will review current treatment recommendations and future directions for both research and practice. We argue that the integration of biological and behavioral approaches will be critical to sufficiently address why these comorbidities exist and how they can best be targeted in treatment.

  15. Fluid mechanics in dentinal microtubules provides mechanistic insights into the difference between hot and cold dental pain.

    Science.gov (United States)

    Lin, Min; Luo, Zheng Yuan; Bai, Bo Feng; Xu, Feng; Lu, Tian Jian

    2011-03-23

    Dental thermal pain is a significant health problem in daily life and dentistry. There is a long-standing question regarding the phenomenon that cold stimulation evokes sharper and more shooting pain sensations than hot stimulation. This phenomenon, however, outlives the well-known hydrodynamic theory used to explain dental thermal pain mechanism. Here, we present a mathematical model based on the hypothesis that hot or cold stimulation-induced different directions of dentinal fluid flow and the corresponding odontoblast movements in dentinal microtubules contribute to different dental pain responses. We coupled a computational fluid dynamics model, describing the fluid mechanics in dentinal microtubules, with a modified Hodgkin-Huxley model, describing the discharge behavior of intradental neuron. The simulated results agreed well with existing experimental measurements. We thence demonstrated theoretically that intradental mechano-sensitive nociceptors are not "equally sensitive" to inward (into the pulp) and outward (away from the pulp) fluid flows, providing mechanistic insights into the difference between hot and cold dental pain. The model developed here could enable better diagnosis in endodontics which requires an understanding of pulpal histology, neurology and physiology, as well as their dynamic response to the thermal stimulation used in dental practices.

  16. Spinal mechanical load as a risk factor for low back pain: A systematic review of prospective cohort studies

    NARCIS (Netherlands)

    E.W.P. Bakker; A.P. Verhagen; E. van Trijffel; C. Lucas; B.W. Koes

    2009-01-01

    Study Design. Systematic review. Objective. To review and critically evaluate the past literature for spinal mechanical load as risk factor for low back pain (LBP). Summary of Background Data. LBP is a costly health problem worldwide, and treatments are often unsuccessful. Therefore, prevention migh

  17. Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain

    Institute of Scientific and Technical Information of China (English)

    Asbj(φ)rn Mohr Drewes; Lars Arendt-Nielsen; Peter Funch-Jensen; Hans Gregersen

    2006-01-01

    Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy.

  18. THE CRUCIAL ROLE OF CENTRAL BANK TRANSPARENCY IN ASSESSING THE MONETARY POLICY COMMITTEE MECHANISM

    Directory of Open Access Journals (Sweden)

    Dumiter Florin Cornel

    2012-12-01

    Full Text Available In the past, central banks used to be very reserved regarding their activities, strategies and monetary policy decisions and actions. As central banks become more and more independent, transparency gained importance based upon accountability arguments. An important fact for adopting an increasing central bank transparency lies in its importance of influencing the development of expectations. The concept of central bank transparency has emerged in the economic literature relatively later than some other key concepts. The widespread agreement of an inflation targeting regime and a more transparent central bank is desired by the most central banks around the world in the context of the need of the public disclosure of macroeconomic models, the quarterly time series for indicators like: inflation, output, budgetary deficit, public debt, interest rate, inflation expectations, the public announcement of the monetary policy decisions, objectives and targets, the publication of some key monetary tools like: inflation report, financial stability report, monetary policy committee report, annual report. These are all key issues in the construction of a more transparent and independent central bank in the context of a good global governance. Moreover, for the fruitful success of the central bank, latum sensu, and monetary policy, stricto sensu, it must be encompassed a complex monetary policy committee mechanism. This complex mechanism must by edowed with the collegial approach of the monetary policy committee, structure of the voting mechanism within the committee, the importance of the person which announces the changes within the interest rates and the public disclosure of these information’s enriched in a communication strategy. This communication strategy is very important for assessing and public understanding of the central bank’s actions but also for communicating the objectives, targets and forward looking approaches of the monetary

  19. Neurophysiological mechanisms in acceptance and commitment therapy in opioid-addicted patients with chronic pain.

    Science.gov (United States)

    Smallwood, Rachel F; Potter, Jennifer S; Robin, Donald A

    2016-04-30

    Acceptance and Commitment Therapy (ACT) has been effectively utilized to treat both chronic pain and substance use disorder independently. Given these results and the vital need to treat the comorbidity of the two disorders, a pilot ACT treatment was implemented in individuals with comorbid chronic pain and opioid addiction. This pilot study supported using neurophysiology to characterize treatment effects and revealed that, following ACT, participants with this comorbidity exhibited reductions in brain activation due to painful stimulus and in connectivity at rest.

  20. Descending inhibitory pain modulation is impaired in patients with chronic pancreatitis.

    NARCIS (Netherlands)

    Olesen, S.S.; Brock, C.; Krarup, A.L.; Funch-Jensen, P.; Arendt-Nielsen, L.; Wilder-Smith, O.H.G.; Drewes, A.M.

    2010-01-01

    BACKGROUND & AIMS: Pain is a prominent symptom in chronic pancreatitis (CP), but the underlying mechanisms are incompletely understood. We investigated the role of descending pain modulation from supraspinal structures as well as central nervous system sensitization in patients with pain from CP. ME

  1. Assessment of Pain Response in Capsaicin-Induced Dynamic Mechanical Allodynia Using a Novel and Fully Automated Brushing Device

    Directory of Open Access Journals (Sweden)

    Kristian G du Jardin

    2013-01-01

    Full Text Available BACKGROUND: Dynamic mechanical allodynia is traditionally induced by manual brushing of the skin. Brushing force and speed have been shown to influence the intensity of brush-evoked pain. There are still limited data available with respect to the optimal stroke number, length, force, angle and speed. Therefore, an automated brushing device (ABD was developed, for which brushing angle and speed could be controlled to enable quantitative assessment of dynamic mechanical allodynia.

  2. The influence of a series of five dry cupping treatments on pain and mechanical thresholds in patients with chronic non-specific neck pain - a randomised controlled pilot study

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    Dobos Gustav J

    2011-08-01

    Full Text Available Abstract Background In this preliminary trial we investigated the effects of dry cupping, an ancient method for treating pain syndromes, on patients with chronic non-specific neck pain. Sensory mechanical thresholds and the participants' self-reported outcome measures of pain and quality of life were evaluated. Methods Fifty patients (50.5 ± 11.9 years were randomised to a treatment group (TG or a waiting-list control group (WL. Patients in the TG received a series of 5 cupping treatments over a period of 2 weeks; the control group did not. Self-reported outcome measures before and after the cupping series included the following: Pain at rest (PR and maximal pain related to movement (PM on a 100-mm visual analogue scale (VAS, pain diary (PD data on a 0-10 numeric rating scale (NRS, Neck Disability Index (NDI, and health-related quality of life (SF-36. In addition, the mechanical-detection thresholds (MDT, vibration-detection thresholds (VDT, and pressure-pain thresholds (PPT were determined at pain-related and control areas. Results Patients of the TG had significantly less pain after cupping therapy than patients of the WL group (PR: Δ-22.5 mm, p = 0.00002; PM: Δ-17.8 mm, p = 0.01. Pain diaries (PD revealed that neck pain decreased gradually in the TG patients and that pain reported by the two groups differed significantly after the fifth cupping session (Δ-1.1, p = 0.001. There were also significant differences in the SF-36 subscales for bodily pain (Δ13.8, p = 0.006 and vitality (Δ10.2, p = 0.006. Group differences in PPT were significant at pain-related and control areas (all p Conclusions A series of five dry cupping treatments appeared to be effective in relieving chronic non-specific neck pain. Not only subjective measures improved, but also mechanical pain sensitivity differed significantly between the two groups, suggesting that cupping has an influence on functional pain processing. Trial registration The trial was registered at

  3. The outcome of control groups in clinical trials of conservative treatments for chronic mechanical neck pain: a systematic review

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    Hagino Carol

    2006-07-01

    Full Text Available Abstract Background Chronic neck pain is highly prevalent in Western societies, with about 15% of females and 10% of males suffering with it at any time. The course of untreated chronic neck pain patients in clinical trials has not been well-defined and the placebo effect has not been clarified. Methods A systematic review of RCT's of conservative treatments for chronic mechanical neck pain was conducted. Studies were excluded if they did not include a control group, if they involved subjects with whiplash injuries, a predominance of headache or arm pain associated with chronic neck pain and if only one treatment was reported. Only studies scoring 3–5 out of 5 on the Jadad Scale for quality were included in the final analysis. Data on change in pain scores of subjects in both placebo (PL as well as no-treatment (NT control groups were analyzed. Mean changes in pain scores as well as effect sizes were calculated, summarized and compared between these groups. Results Twenty (20 studies, 5 in the NT group and 15 in the PL group, with outcome intervals ranging from 1–52 weeks were included in the final analysis. The mean [95% CI] effect size of change in pain ratings in the no-treatment control studies at outcome points up to 10 weeks was 0.18 [-0.05, 0.41] and for outcomes from 12–52 weeks it was 0.4 [0.12, 0.68]. In the placebo control groups it was 0.50 [0.10, 0.90] at up to 10 weeks and 0.33. [-1.97, 2.66] at 12–24 weeks. None of the comparisons between the no-treatment and placebo groups were statistically significant. Conclusion It appears that the changes in pain scores in subjects with chronic neck pain not due to whiplash who are enrolled in no-treatment and placebo control groups were similarly small and not significantly different. As well, they do not appear to increase over longer-term follow-up.

  4. Comparing Physical Therapy Accompanying Exercise with Only Exercise Treatments in Patients with Chronic Mechanical Low Back Pain

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    Özlem Yılmaz

    2015-08-01

    Full Text Available Objective: Investigating and comparing the effects of exercise and physical therapy accompanying exercise treatments in patients with chronic low back pain. Materials and Methods: Twenty three patients with mechanical type low back existing more than 3 months were included one of the exercise or the physical therapy+exercise groups according to their application sequence. Both of the groups performed lumbar flexion and extension exercises, strengthening of the lumbar and abdominal muscle exercises and iliopsoas, hamstring and quadriceps stretching exercises two times a day for 14 days. The physical therapy group was given hot pack+therapeutic ultrasound+ interferential current for 10 days additionally. Degree of the low back pain was evaluated with visual analog scale (VAS, range of joint motion was evaluated with hand finger floor distance (HFFD and Modified Schober test, functional status was evaluated with Modified Oswestry Low Back Pain Scale and quality of life was evaluated with Short form-36 (SF-36 before and a month after the treatments. Results: In both groups (exercise group: average age 59 years, 21 females, 2 males; physical therapy group: average age 60 years, 20 females, 3 males pain intensity and HFFD decreased and Modified Schober increased, functionality recovered, pain and physical functions of SF-36 improved after the treatments. SF-36-physical role difficulty also improved in the exercise group. Decrease in pain, increase in HFFD andimproving of the functional status were all significantly more in the physical therapy group. There were no difference between the groups in terms of Modified Schober measurement and changes of the quality of life. Conclusions: Exercises and exercise+physical therapy are both effective in chronic low back pain. Successful results can be taken by addition of the physical therapy in patients who do not benefit sufficiently from exercise therapy. (Turkish Journal of Osteoporosis 2015;21: 73-8

  5. Pavlovian conditioning of opioid and nonopioid pain inhibitory mechanisms in humans.

    Science.gov (United States)

    Flor, Herta; Birbaumer, Niels; Schulz, Robin; Grüsser, Sabine M; Mucha, Ronald F

    2002-01-01

    Learning processes such as respondent or Pavlovian conditioning are believed to play an important role in the development of chronic pain, however, their influence on the inhibition of pain has so far not been assessed in humans. The purpose of this study was the demonstration of Pavlovian conditioning of stress-induced analgesia in humans and the determination of its opioid mediation. In a differential classical conditioning paradigm two different auditory stimuli served as conditioned stimuli and mental arithmetic plus white noise as unconditioned stimulus. Subsequent to four conditioning trials naloxone or placebo was applied in a double-blind fashion on two test days. Both pain threshold and pain tolerance showed conditioned stress-induced analgesia. Pain tolerance was affected by naloxone whereas pain threshold was not. The data of this study show that stress analgesia can be conditioned in humans and that it is at least partially mediated by the endogenous opioid system. Learning processes also influence pain inhibitory processes in humans and this effect might play a role in the development of chronic pain.

  6. 神经病理性疼痛的机制分类与治疗策略%Pathophysiological mechanisms and therapeutic options of neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    陈雪梅; 许今; 王祥瑞

    2013-01-01

    Background Being an intractable and chronic syndrome that may arise from injury to somatosensory system,neuropathic pain (NP) seriously affects the life quality of patients.Objective This review presents recent progress in the pathophysiological mechanisms,diagnosis and therapeutic options for NP.Content Five aspects of maladaptive changes in the peripheral,central and autonomic nervous system are focused to illustrate the pathophysiological mechanisms:sensitization of nociceptors,abnormal ectopic excitability of affected neurons and disinhibition of nociception in the spinal inhibitory network,pronociceptive facilitation of the spinal dorsal horn,sympathetically maintained pain,as well as central nervous systerm reorganization processes.Recent progress of diagnosis,pharmacologic treatment and nonpharmacologic treatment of NP are also discussed.Trend A better understanding of pathophysiological mechanisms of NP will leads to a more effective and specific mechanism-based treatment approach.%背景 神经病理性疼痛(neuropathic pain,NP)是由于躯体感觉系统受损或病变而导致的顽固性疼痛,是严重影响患者生活质量的疾病. 目的 综述NP的发病机制、诊断与治疗的最新进展. 内容 从伤害感受器的敏感性增加、传入神经的异常电活动及中枢失抑制、脊髓背角变化促进伤害性感觉、交感系统对于伤害性感觉的维持和中枢重构5个方面阐述NP的发病机制,简介诊断方法,并从药物与非药物治疗的角度介绍现有的治疗方法. 趋向 根据发病机制的不同进行分类并采取相应的治疗措施将成为未来NP的防治方向,为患者提供更有效和精准的治疗策略.

  7. Glial involvement in trigeminal central sensitization

    Institute of Scientific and Technical Information of China (English)

    Yu-feng XIE

    2008-01-01

    Recent studies have indicated that trigeminal neurons exhibit central sensitization, an increase in the excitability of neurons within the central nervous system to the extent that a normally innocuous stimulus begins to produce pain after inflamma-tion or injury, and that glial activities play a vital role in this central sensitization. The involvement of glial cells in trigeminal central sensitization contains multiple mechanisms, including interaction with glutamatergic and purinergic receptors. A better understanding of the trigeminal central sensitization mediated by glial cells will help to find potential therapeutic targets and lead to developing new analge-sics for orofacial-specific pain with higher efficiency and fewer side-effects.

  8. Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch

    Science.gov (United States)

    Anand, P.; Bley, K.

    2011-01-01

    Summary Topical capsaicin formulations are used for pain management. Safety and modest efficacy of low-concentration capsaicin formulations, which require repeated daily self-administration, are supported by meta-analyses of numerous studies. A high-concentration capsaicin 8% patch (Qutenza™) was recently approved in the EU and USA. A single 60-min application in patients with neuropathic pain produced effective pain relief for up to 12 weeks. Advantages of the high-concentration capsaicin patch include longer duration of effect, patient compliance, and low risk for systemic effects or drug–drug interactions. The mechanism of action of topical capsaicin has been ascribed to depletion of substance P. However, experimental and clinical studies show that depletion of substance P from nociceptors is only a correlate of capsaicin treatment and has little, if any, causative role in pain relief. Rather, topical capsaicin acts in the skin to attenuate cutaneous hypersensitivity and reduce pain by a process best described as ‘defunctionalization’ of nociceptor fibres. Defunctionalization is due to a number of effects that include temporary loss of membrane potential, inability to transport neurotrophic factors leading to altered phenotype, and reversible retraction of epidermal and dermal nerve fibre terminals. Peripheral neuropathic hypersensitivity is mediated by diverse mechanisms, including altered expression of the capsaicin receptor TRPV1 or other key ion channels in affected or intact adjacent peripheral nociceptive nerve fibres, aberrant re-innervation, and collateral sprouting, all of which are defunctionalized by topical capsaicin. Evidence suggests that the utility of topical capsaicin may extend beyond painful peripheral neuropathies. PMID:21852280

  9. ANALYSIS OF THE PATHOGENETIC MECHANISMS OF CHRONIC JOINT PAIN IN PATIENTS WITH RHEUMATOID ARTHRITIS AND KNEE OSTEOARTHRITIS

    Directory of Open Access Journals (Sweden)

    E. S. Filatova

    2014-01-01

    Full Text Available Objective: to reveal neurogenic mechanisms in the pathogenesis of chronic pain syndrome in rheumatoid arthritis (RA and knee osteoarthritis (OA in order to develop individualized pharmacotherapy.Subjects and methods. One hundred and eighty-three patients with RA and 80 with knee OA were examined. By using the neuropathic pain diagnostic questionnaire (DN4, all the patients were divided into 2 groups with and without a neuropathic pain component (NPC.Results. NPC was found in 43% of the patients with RA and it was connected with involvement of the peripheral somatosensory system. In RA, NPC was common in older patients with longer disease duration, higher X-ray stage, and severe functional insufficiency. 30% of patients with knee OA also had NPC, however the signs of nervous system involvement were absent. In OA, NPC was associated with hyperalgesia, higher pain intensity, more marked joint dysfunction on the WOMAC, and anxiety.Discussion. This investigation revealed a mixed pattern of chronic pain syndrome in patients with RA and knee OA; some patients were found to have a NPC in the presence of predominantly a nociceptive component

  10. Mechanisms underlying ectopic persistent tooth-pulp pain following pulpal inflammation.

    Science.gov (United States)

    Matsuura, Shingo; Shimizu, Kohei; Shinoda, Masamichi; Ohara, Kinuyo; Ogiso, Bunnai; Honda, Kuniya; Katagiri, Ayano; Sessle, Barry J; Urata, Kentaro; Iwata, Koichi

    2013-01-01

    In order to clarify the peripheral mechanisms of ectopic persistent pain in a tooth pulp following pulpal inflammation of an adjacent tooth, masseter muscle activity, phosphorylated extracellular signal-regulated protein kinase (pERK) and TRPV1 immunohistochemistries and satellite cell activation using glial fibrillary acidic protein (GFAP) immunohistochemistry in the trigeminal ganglion (TG) were studied in the rats with molar tooth-pulp inflammation. And, Fluorogold (FG) and DiI were also used in a neuronal tracing study to analyze if some TG neurons innervate more than one tooth pulp. Complete Freund's adjuvant (CFA) or saline was applied into the upper first molar tooth pulp (M1) in pentobarbital-anesthetized rats, and capsaicin was applied into the upper second molar tooth pulp (M2) on day 3 after the CFA or saline application. Mean EMG activity elicited in the masseter muscle by capsaicin application to M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. The mean number of pERK-immunoreactive (IR) TG cells was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. Application of the satellite cell inhibitor fluorocitrate (FC) into TG caused a significant depression of capsaicin-induced masseter muscle activity and a significant reduction of satellite cell activation. The number of TRPV1-IR TG cells innervating M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats, and that was decreased following FC injection into TG. Furthermore, 6% of TG neurons innervating M1 and/or M2 innervated both M1 and M2. These findings suggest that satellite cell activation following tooth pulp inflammation and innervation of multiple tooth pulps by single TG neurons may be involved in the enhancement of the activity of TG neurons innervating adjacent non-inflamed teeth that also show enhancement of TRPV1 expression in TG neurons, resulting in the ectopic persistent tooth-pulp pain

  11. Mechanisms underlying ectopic persistent tooth-pulp pain following pulpal inflammation.

    Directory of Open Access Journals (Sweden)

    Shingo Matsuura

    Full Text Available In order to clarify the peripheral mechanisms of ectopic persistent pain in a tooth pulp following pulpal inflammation of an adjacent tooth, masseter muscle activity, phosphorylated extracellular signal-regulated protein kinase (pERK and TRPV1 immunohistochemistries and satellite cell activation using glial fibrillary acidic protein (GFAP immunohistochemistry in the trigeminal ganglion (TG were studied in the rats with molar tooth-pulp inflammation. And, Fluorogold (FG and DiI were also used in a neuronal tracing study to analyze if some TG neurons innervate more than one tooth pulp. Complete Freund's adjuvant (CFA or saline was applied into the upper first molar tooth pulp (M1 in pentobarbital-anesthetized rats, and capsaicin was applied into the upper second molar tooth pulp (M2 on day 3 after the CFA or saline application. Mean EMG activity elicited in the masseter muscle by capsaicin application to M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. The mean number of pERK-immunoreactive (IR TG cells was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. Application of the satellite cell inhibitor fluorocitrate (FC into TG caused a significant depression of capsaicin-induced masseter muscle activity and a significant reduction of satellite cell activation. The number of TRPV1-IR TG cells innervating M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats, and that was decreased following FC injection into TG. Furthermore, 6% of TG neurons innervating M1 and/or M2 innervated both M1 and M2. These findings suggest that satellite cell activation following tooth pulp inflammation and innervation of multiple tooth pulps by single TG neurons may be involved in the enhancement of the activity of TG neurons innervating adjacent non-inflamed teeth that also show enhancement of TRPV1 expression in TG neurons, resulting in the ectopic persistent tooth

  12. TMD and chronic pain: A current view

    Science.gov (United States)

    Furquim, Bruno D'Aurea; Flamengui, Lívia Maria Sales Pinto; Conti, Paulo César Rodrigues

    2015-01-01

    This review aims at presenting a current view on the physiopathologic mechanisms associated with temporomandibular disorders (TMDs). While joint pain is characterized by a well-defined inflammatory process mediated by tumor necrosis factor-α and interleukin, chronic muscle pain presents with enigmatic physiopathologic mechanisms, being considered a functional pain syndrome similar to fibromyalgia, irritable bowel syndrome, interstitial cystitis and chronic fatigue syndrome. Central sensitization is the common factor unifying these conditions, and may be influenced by the autonomic nervous system and genetic polymorphisms. Thus, TMDs symptoms should be understood as a complex response which might get worse or improve depending on an individual's adaptation. PMID:25741834

  13. TMD and chronic pain: A current view

    Directory of Open Access Journals (Sweden)

    Bruno D'Aurea Furquim

    2015-02-01

    Full Text Available This review aims at presenting a current view on the physiopathologic mechanisms associated with temporomandibular disorders (TMDs. While joint pain is characterized by a well-defined inflammatory process mediated by tumor necrosis factor-α and interleukin, chronic muscle pain presents with enigmatic physiopathologic mechanisms, being considered a functional pain syndrome similar to fibromyalgia, irritable bowel syndrome, interstitial cystitis and chronic fatigue syndrome. Central sensitization is the common factor unifying these conditions, and may be influenced by the autonomic nervous system and genetic polymorphisms. Thus, TMDs symptoms should be understood as a complex response which might get worse or improve depending on an individual's adaptation.

  14. Central NMDA Receptor Function in Pain and Intervention of Ele-acupuncture%中枢NMDA受体在疼痛中的作用及电针的干预研究

    Institute of Scientific and Technical Information of China (English)

    梁宜; 方剑乔; 房军帆; 杜俊英; 邱宇洁; 刘晋; 董娴蔚; 王佳

    2012-01-01

    NMDA receptor belongs to ionic glutamic acid; it participates in many physiological and pathological courses and exerts great function. Recent study shows that central NMDA receptor concerns pain occurrence and development. Ele-acupuncture is one of the common ways in clinical analgesia. The article summarizes central NMDA function in pain and ele -acupunture analgesia, hoping to offer foundation to expound NMDA receptor intervention mechanism of ele-acupunture analgesia.%N-甲基-D-天冬氨酸(NMDA)受体属于离子型谷氨酸受体之一,参与多种生理和病理过程并发挥重要作用.近来研究表明,中枢 NMDA受体参与疼痛的发生和发展.电针是目前临床用于镇痛的常用手段之一,本文综述了中枢NMDA在疼痛和电针镇痛中的作用,以期为 阐释电针镇痛的NMDA受体干预机制提供依据.

  15. Dental restoration induced orofacial pain and its management

    Directory of Open Access Journals (Sweden)

    Xiuxin Liu

    2015-01-01

    Full Text Available Dental procedure induced pain may develop into a chronic condition that accompanied with functional or neuropathy changes in the nerve system. In this case, severe persistent pain gradually developed after repeatedly placing a subgingival amalgam restoration in the right second molar. Hyperalgesia and allodynia were present at the affected region. A provisional diagnosis of chronic orofacial pain with peripheral and central sensitization was considered. After re-contouring, local debridement and occlusal adjustment the pain disappeared. The underlying mechanism in this case is neuronal sensitization and peripheral Aβ-fiber mechanoreceptor activation. Its diagnosis and management depend on identification and treatment of the cause for pain generation and sensitization.

  16. Spinal high-mobility group box 1 contributes to mechanical allodynia in a rat model of bone cancer pain

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Wei [Department of Out-Patient, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Wang, Wei; Huang, Jing [Department of Anatomy and K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi' an 710032 (China); Ren, Ning [Comprehensive Diagnostic and Therapeutic Center, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Wu, Sheng-Xi, E-mail: shengxi@fmmu.edu.cn [Department of Anatomy and K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi' an 710032 (China); Li, Yong-Qi, E-mail: devneuro@fmmu.edu.cn [Comprehensive Diagnostic and Therapeutic Center, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China)

    2010-05-14

    Mechanisms underlying bone cancer-induced pain are largely unknown. Previous studies indicate that neuroinflammation in the spinal dorsal horn is especially involved. Being first reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a mediator of inflammation. We hypothesized that HMGB1 could trigger the release of cytokines in the spinal dorsal horn and contribute to bone cancer pain. To test this hypothesis, we first built a bone cancer pain model induced by intratibal injection of Walker 256 mammary gland carcinoma cells. The structural damage to the tibia was monitored by radiological analysis. The mechanical allodynia was measured and the expression of spinal HMGB1 and IL-1{beta} was evaluated. We observed that inoculation of cancer cells, but not heat-killed cells, induced progressive bone destruction from 9 d to 21 d post inoculation. Behavioral tests demonstrated that the significant nociceptive response in the cancer cells-injected rats emerged on day 9 and this kind of mechanical allodynia lasted at least 21 d following inoculation. Tumor cells inoculation significantly increased HMGB1 expression in the spinal dorsal horn, while intrathecal injecting a neutralizing antibody against HMGB1 showed an effective and reliable anti-allodynia effect with a dose-dependent manner. IL-1{beta} was significantly increased in caner pain rats while intrathecally administration of anti-HMGB1 could decrease IL-1{beta}. Together with previous reports, we predict that bone cancer induces HMGB1 production, enhancing spinal IL-1{beta} expression and thus modulating spinal excitatory synaptic transmission and pain response.

  17. Altered pain perception in children with chronic tension-type headache: Is this a sign of central sensitisation?

    DEFF Research Database (Denmark)

    Soee, AL; Thomsen, LL; Kreiner, S

    2013-01-01

    The aim of this article is to investigate if children (7-17 years) with frequent episodic tension-type headache (FETTH) or chronic TTH (CTTH) have an altered pain perception compared to healthy controls.......The aim of this article is to investigate if children (7-17 years) with frequent episodic tension-type headache (FETTH) or chronic TTH (CTTH) have an altered pain perception compared to healthy controls....

  18. Flow confirmation study for central venous port in oncologic outpatient undergoing chemotherapy: Evaluation of suspected system-related mechanical complications

    Energy Technology Data Exchange (ETDEWEB)

    Sofue, Keitaro, E-mail: ksofue@ncc.go.jp [Divisions of Diagnostic Radiology, National Cancer Center Hospital (Japan); Department of Radiology, Kobe University, Graduate School of Medicine (Japan); Arai, Yasuaki; Takeuchi, Yoshito [Divisions of Diagnostic Radiology, National Cancer Center Hospital (Japan); Sugimura, Kazuro [Department of Radiology, Kobe University, Graduate School of Medicine (Japan)

    2013-11-01

    Purpose: To evaluate the efficacy and outcome of a flow confirmation study (FCS) in oncologic outpatients undergoing chemotherapy suspected of a central venous port (CVP) system-related mechanical complication. Materials and methods: A total of 66 patients (27 men, 39 women; mean age, 60 years) received FCS for the following reasons: prolonged infusion time during chemotherapy (n = 32), inability to inject saline fluid (n = 15), lateral neck and/or back pain (n = 6), subcutaneous extravasation of anticancer drug (n = 5), arm swelling (n = 4), and inability to puncture the port (n = 4). FCS consisted of examining the position of CVP, potential secondary shifts or fractures, and integrity of the system using contrast material through the port. Results: Of the 66 patients, 43 had an abnormal finding uncovered by FCS. The most frequent abnormal findings was catheter kinking (n = 22). Explantation and reimplantation of the CVP system was required in 21 of the 66 patients. Remaining 45 patients were able continue using the CVP system after the FCS without any system malfunction. Conclusion: FCS was effective for evaluating CVP system-related mechanical complications and was useful for deciding whether CVP system explantation and reimplantation was required.

  19. Performance, pain, and quality of life on use of central venous catheter for management of pericardial effusions in patients undergoing coronary artery bypass graft surgery

    Directory of Open Access Journals (Sweden)

    Ghods K

    2016-10-01

    Full Text Available Kamran Ghods,1 Mohammad Reza Razavi,2 Mohammad Forozeshfard3 1Clinical Research Development Unit (CRDU, Department of Cardiovascular Surgery, Kowsar Hospital, 2Nursing Care Research Center, 3Cancer Research Center, Department of Anesthesiology, Semnan University of Medical Sciences, Semnan, Iran Abstract: Different pericardial catheters have been suggested as an effective alternative method for drainage of pericardial effusion. The aim of this study was to determine the performance, pain, and quality of life on use of central venous catheter (CVC for drainage of pericardial effusion in patients undergoing open heart surgery. Fifty-five patients who had developed pericardial effusion after an open heart surgery (2012–2015 were prospectively assessed. Triple-lumen central catheters were inserted under echocardiographic guidance. Clinical, procedural, complication, and outcome details were analyzed. Intensity of pain and quality of life of patients were assessed using the numerical rating scale and Short-Form Health Survey. CVC was inserted for 36 males and 19 females, all of whom had a mean age of 58.5±15 years, and the mean duration of the open heart surgery was 8±3.5 hours. The mean central venous pressure catheter life span was 14.6 days. No cases of recurrent effusion and complication were reported. The technical success rate of procedure was 100%. Intensity of pain and quality of life of patients had improved during follow-up. CVC insertion is a safe and effective technique for the management of pericardial effusion in patients after open heart surgery. Keywords: coronary artery bypass graft, pericardial effusion, central venous catheter

  20. Acute effects of single and multiple level thoracic manipulations on chronic mechanical neck pain: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Puntumetakul R

    2015-01-01

    Full Text Available Rungthip Puntumetakul,1,2 Thavatchai Suvarnnato,1,3 Phurichaya Werasirirat,1 Sureeporn Uthaikhup,2 Junichiro Yamauchi,4,5 Rose Boucaut6 1School of Physical Therapy, Faculty of Associated Medical Sciences, 2Research Center in Back, Neck, Other Joint Pain and Human Performance, 3Physical Therapy Unit, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; 4Graduate School of Human Health Sciences, Tokyo Metropolitan University, 5Future Institute for Sport Sciences, Tokyo, Japan; 6School of Health Sciences (Physiotherapy, University of South Australia, Adelaide, SA, Australia Background: Thoracic spine manipulation has become a popular alternative to local cervical manipulative therapy for mechanical neck pain. This study investigated the acute effects of single-level and multiple-level thoracic manipulations on chronic mechanical neck pain (CMNP.Methods: Forty-eight patients with CMNP were randomly allocated to single-level thoracic manipulation (STM at T6–T7 or multiple-level thoracic manipulation (MTM, or to a control group (prone lying. Cervical range of motion (CROM, visual analog scale (VAS, and the Thai version of the Neck Disability Index (NDI-TH scores were measured at baseline, and at 24-hour and at 1-week follow-up.Results: At 24-hour and 1-week follow-up, neck disability and pain levels were significantly (P<0.05 improved in the STM and MTM groups compared with the control group. CROM in flexion and left lateral flexion were increased significantly (P<0.05 in the STM group when compared with the control group at 1-week follow-up. The CROM in right rotation was increased significantly after MTM compared to the control group (P<0.05 at 24-hour follow-up. There were no statistically significant differences in neck disability, pain level at rest, and CROM between the STM and MTM groups.Conclusion: These results suggest that both single-level and multiple-level thoracic manipulation improve neck disability

  1. Hypersensitivity to mechanical and intra-articular electrical stimuli in persons with painful temporomandibular joints

    DEFF Research Database (Denmark)

    Ayesh, Emad; Jensen, Troels Staehelin; Svensson, P

    2007-01-01

    This study tested whether persons with TMJ arthralgia have a modality-specific and site-specific hypersensitivity to somatosensory stimuli assessed by quantitative sensory tests (QST). Forty-three healthy persons and 20 with TMJ arthralgia participated. The QST consisted of: sensory and pain...... detection thresholds and summation threshold to intra-articular electrical stimulation, tactile and pin-prick sensitivity in the TMJ area, pressure-pain threshold and tolerance on the lateral side of the TMJ and on the finger. Persons with TMJ arthralgia had lower pain detection and summation thresholds (P...

  2. [Types of topical treatment for peripheral neuropathic pain : Mechanism of action and indications].

    Science.gov (United States)

    Baron, R; Mahn, F

    2010-08-01

    The term "peripheral neuropathic pain syndromes" summarizes several chronic pain syndromes, which can occur focally or generalized in the peripheral nervous system in the course of an impairment of afferent neurons. Controlled clinical trials gave distinct indications for systemic treatments with antidepressants, anticonvulsants and opioid analgesics in several neuropathic pain syndromes. In addition to these systemic therapies, there are also two topical treatment options: topical application of lidocaine and capsaicin. An important cause of sensitization phenomena of afferent nociceptors is the upregulation of sodium channels and thermosensor channels. In the context of a partial nerve lesion that leaves behind partially preserved or regenerated afferent nerve fibres, just these channels could be used as target structures for topical medications. Topically applied drugs are absorbed systemically only in minute quantities, so systemic side effects are negligible. Pharmacological interactions with systematically acting substances are also virtually absent; thus, topically applied substances are especially appropriate for add-on therapy in addition to systemic pain medication.

  3. [Fetal pain - neurobiological causes and consequences].

    Science.gov (United States)

    Gonçalves, Nuno; Rebelo, Sandra; Tavares, Isaura

    2010-01-01

    The existence of putatively painful situations to the fetus demands a careful evaluation of the issue of fetal pain. Several indirect approaches are used to evaluate the existence of fetal pain. Neurobiological studies showed that from the 30th week on, the anatomical and physiological system for pain transmission is already developed, with the connections from the periphery to the cortex being successively established. Stress responses to a painful stimulation are complex but they can be detected from the 16th week on. There is activation of the hypothalamus-pituitary-adrenal axis, autonomic nervous system and hemodynamic changes in response to nociceptive stimulation. In prematures exposed to pain there are significant increases of adrenaline, noradrenaline and cortisol, hemodynamic changes, motor reflexes and facial reactions. The changes induced by strong nociceptive stimulation of newborns have important postnatal consequences since they affect future reactions to noxious stimuli. Central sensitization and immaturity of the pain inhibitory system are the main neurobiological explanations for the increased pain. Detailed studies of the neurobiological mechanisms of the transmission of painful stimuli along with follow-up studies of the consequences of exposure to pain during the development of the fetus are necessary to fully understand fetal pain.

  4. Pain and Nociception

    DEFF Research Database (Denmark)

    Falk, Sarah; Dickenson, Anthony H

    2014-01-01

    Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic. As detection and survival among patients with cancer have improved, pain has become an increasing challenge, because traditional...... therapies are often only partially effective. Until recently, knowledge of cancer pain mechanisms was poor compared with understanding of neuropathic and inflammatory pain states. We now view cancer-induced bone pain as a complex pain state involving components of both inflammatory and neuropathic pain...... but also exhibiting elements that seem unique to cancer pain. In addition, the pain state is often unpredictable, and the intensity of the pain is highly variable, making it difficult to manage. The establishment of translational animal models has started to reveal some of the molecular components involved...

  5. A COMPARATIVE STUDY TO FIND OUT THE EFFECTIVENESS BETWEEN CORE STABILIZATION VS MCKENZIE EXERCISES IN THE TREATMENT OF PATIENTS WITH MECHANICAL LOW BACK PAIN

    Directory of Open Access Journals (Sweden)

    Abhijit Dutta

    2015-10-01

    Full Text Available Background: Mechanical Low back pain is a leading cause of disability. It occurs in similar proportions in all cultures, interferes with quality of life and work performance. Both male and female populations are affected; however, there is a tendency towards a higher incidence in male patients. Mechanical low back pain is associated with pain and clinical instability in lumbar motion segments. Exercises play an important part in the rehabilitation of low back pain. The aim of this study was to compare the effectiveness between Core stabilization vs McKenzie exercises in the treatment of patients with mechanical low back pain. Methods: 30 patients were selected between the age groups of 20 yrs to 50 yrs and having a past history of low back pain for one month. 15 patients were allotted to each group of experiment. Group I was given Core stabilization exercises and Group II with McKenzie exercises. Interferential therapy was a common treatment for both the groups. Evaluations of the subjects were done using the Revised Oswestry Disability Index and Dynamic Endurance tests. Results: Data analysis revealed statistically significant difference between both the groups (p<0.05 and proved that Core stabilization exercises is more effective than McKenzie exercises in mechanical low back pain. Conclusion: This study shows that core stabilization exercises possess a greater potential over McKenzie exercises in treating Mechanical Low back pain patients.

  6. The Pronociceptive Effect of Paradoxical Sleep Deprivation in Rats: Evidence for a Role of Descending Pain Modulation Mechanisms.

    Science.gov (United States)

    Tomim, Dabna H; Pontarolla, Felipe M; Bertolini, Jessica F; Arase, Mauricio; Tobaldini, Glaucia; Lima, Marcelo M S; Fischer, Luana

    2016-04-01

    The mechanisms underlying the pronociceptive effect of paradoxical sleep deprivation (PSD) are not known. In this study, we asked whether PSD increases tonic nociception in the formalin test, decreases the antinociceptive effect of morphine administered into the periaqueductal gray matter (PAG), and disrupts endogenous descending pain modulation. PSD for either 24 or 48 h significantly increased formalin-induced nociception and decreased mechanical nociceptive paw withdrawal threshold. The maximal antinociceptive effect induced by morphine (0.9-9 nmol, intra-PAG) was significantly decreased by PSD. The administration of a low dose of the GABAA receptor antagonist, bicuculline (30-300 pmol, intra-PAG), decreased nociception in control rats, but not in paradoxical-sleep-deprived ones. Furthermore, the administration of the cholecystokinin (CCK) 2 receptor antagonist, YM022 (0.5-2 pmol) in the rostral ventral medulla (RVM), decreased nociception in paradoxical-sleep-deprived rats but not in control ones. While a dose of the CCK 2 receptor agonist, CCK-8 (8-24 pmol intra-RVM), increased nociception in control rats, but not in paradoxical-sleep-deprived ones. In addition, the injection of lidocaine (QX-314, 2%, intra-RVM) decreased nociception in sleep-deprived rats, but not in control rats, while the lesion of the dorsolateral funiculus prevented the pronociceptive effect of PSD. Finally, PSD significantly increased c-Fos expression in the RVM. Therefore, PSD increases pain independently of its duration or of the characteristic of the nociceptive stimulus and decreases morphine analgesia at the PAG. PSD appears to increase pain by decreasing descending pain inhibitory activity and by increasing descending pain facilitatory activity.

  7. Antinociceptive effects of fisetin against diabetic neuropathic pain in mice: Engagement of antioxidant mechanisms and spinal GABAA receptors.

    Science.gov (United States)

    Zhao, Xin; Li, Xin-Lin; Liu, Xin; Wang, Chuang; Zhou, Dong-Sheng; Ma, Qing; Zhou, Wen-Hua; Hu, Zhen-Yu

    2015-12-01

    Peripheral painful neuropathy is one of the most common complications in diabetes and necessitates improved treatment. Fisetin, a naturally occurring flavonoid, has been reported to exert antidepressant-like effect in previous studies. As antidepressant drugs are employed clinically to treat neuropathic pain, this work aimed to investigate whether fisetin possess beneficial effect on diabetic neuropathic pain and explore the mechanism(s). We subjected mice to diabetes by a single intraperitoneal (i.p.) injection of streptozotocin (200mg/kg), and von Frey test or Hargreaves test was used to assess mechanical allodynia or thermal hyperalgesia, respectively. Chronic treatment of diabetic mice with fisetin not only ameliorated the established symptoms of thermal hyperalgesia and mechanical allodynia, but also arrested the development of neuropathic pain when given at low doses. Although chronic fisetin administration did not impact on the symptom of hyperglycemia in diabetic mice, it reduced exacerbated oxidative stress in tissues of spinal cord, dorsal root ganglion (DRG) and sciatic verve. Furthermore, the analgesic actions of fisetin were abolished by repetitive co-treatment with the reactive oxygen species (ROS) donor tert-butyl hydroperoxide (t-BOOH), but potentiated by the ROS scavenger phenyl-N-tert-butylnitrone (PBN). Finally, acute blockade of spinal GABAA receptors by bicuculline totally counteracted such fisetin analgesia. These findings indicate that chronic fisetin treatment can delay or correct neuropathic hyperalgesia and allodynia in mice with type 1 diabetes. Mechanistically, the present fisetin analgesia may be associated with its antioxidant activity, and spinal GABAA receptors are likely rendered as downstream targets.

  8. The influence of repetitive painful stimulation on peripheral and trigeminal pain thresholds.

    Science.gov (United States)

    Dirkwinkel, Monika; Gralow, Ingrid; Colak-Ekici, Reyhan; Wolowski, Anne; Marziniak, Martin; Evers, Stefan

    2008-10-15

    We were interested in how continuous painful stimulation which is performed as inurement exercises in some Asian martial arts influences sensory and pain perception. Therefore, we examined 15 Kung Fu disciples before and after a 14 day period with repetitive inurement exercises and measured sensory and pain thresholds and intensities in both the trigeminal and the peripheral (peroneal nerve) region. The results of the probands were compared to those of 15 healthy control subjects who were performing sports without painful stimulation during this period. The probands showed a significantly decreased trigeminal pain intensity after repetitive electrical stimulation whereas the control subjects did not show any changes of sensory or pain perception during the study period. This suggests a change of central sensitisation and inhibitory control mechanisms in the nociceptive spinal or cerebral pathways by inurement exercises. In addition, pain thresholds showed an (not significant) increase after the study period whereas the control subjects showed a significant decrease of pain thresholds. In summary, our pilot study suggests that inurement exercises, i.e. repetitive painful stimulation, over a period of 14 days might induce changes of pain perception resulting in trigeminal pain habituation and higher pain thresholds.

  9. Is the experience of thermal pain genetics dependent?

    DEFF Research Database (Denmark)

    Horjales-Araujo, Emilia; Dahl, Joergen B

    2015-01-01

    It is suggested that genetic variations explain a significant portion of the variability in pain perception; therefore, increased understanding of pain-related genetic influences may identify new targets for therapies and treatments. The relative contribution of the different genes to the variance...... 26% of the variance in heat pain responses is explained by these variations. Thus, the selection of pain model might markedly influence the magnitude of the association between the pain phenotype and genetic variability. Thermal pain sensation is complex with multiple molecular and cellular...... mechanisms operating alone and in combination within the peripheral and central nervous system. It is thus highly probable that the thermal pain experience is affected by genetic variants in one or more of the pathways involved in the thermal pain signaling. This review aims to present and discuss some...

  10. Pain and modulation processes

    Directory of Open Access Journals (Sweden)

    Ghaffarpoor M

    1997-08-01

    Full Text Available Pain is one of the most important and sometimes difficult problems, that patients and physicians are encountered. It may be clinically acute or chronic, acute pain has usually definite cause and favourable response to treatment. On the other hand there are difficulties in diagnosis and management of chronic pain. Peripheral and cranial nerves convey pain impulses toward central nervous system, and modulations take place at several levels. Diagnosis of different pains, including nociceptive, nerve trunk pain and deafferentation types is essential to acceptable management. In this article we review pain pathway, neurotransmitters and modulation.

  11. Articular dysfunction patterns in patients with mechanical neck pain: a clinical algorithm to guide specific mobilization and manipulation techniques.

    Science.gov (United States)

    Dewitte, Vincent; Beernaert, Axel; Vanthillo, Bart; Barbe, Tom; Danneels, Lieven; Cagnie, Barbara

    2014-02-01

    In view of a didactical approach for teaching cervical mobilization and manipulation techniques to students as well as their use in daily practice, it is mandatory to acquire sound clinical reasoning to optimally apply advanced technical skills. The aim of this Masterclass is to present a clinical algorithm to guide (novice) therapists in their clinical reasoning to identify patients who are likely to respond to mobilization and/or manipulation. The presented clinical reasoning process is situated within the context of pain mechanisms and is narrowed to and applicable in patients with a dominant input pain mechanism. Based on key features in subjective and clinical examination, patients with mechanical nociceptive pain probably arising from articular structures can be categorized into specific articular dysfunction patterns. Pending on these patterns, specific mobilization and manipulation techniques are warranted. The proposed patterns are illustrated in 3 case studies. This clinical algorithm is the corollary of empirical expertise and is complemented by in-depth discussions and knowledge exchange with international colleagues. Consequently, it is intended that a carefully targeted approach contributes to an increase in specificity and safety in the use of cervical mobilizations and manipulation techniques as valuable adjuncts to other manual therapy modalities.

  12. Contemporary views on inflammatory pain mechanisms: TRPing over innate and microglial pathways [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Zhonghui Guan

    2016-09-01

    Full Text Available Tissue injury, whether by trauma, surgical intervention, metabolic dysfunction, ischemia, or infection, evokes a complex cellular response (inflammation that is associated with painful hyperalgesic states. Although in the acute stages it is necessary for protective reflexes and wound healing, inflammation may persist well beyond the need for tissue repair or survival. Prolonged inflammation may well represent the greatest challenge mammalian organisms face, as it can lead to chronic painful conditions, organ dysfunction, morbidity, and death. The complexity of the inflammatory response reflects not only the inciting event (infection, trauma, surgery, cancer, or autoimmune but also the involvement of heterogeneous cell types including neuronal (primary afferents, sensory ganglion, and spinal cord, non-neuronal (endothelial, keratinocytes, epithelial, and fibroblasts, and immune cells. In this commentary, we will examine 1. the expression and regulation of two members of the transient receptor potential family in primary afferent nociceptors and their activation/regulation by products of inflammation, 2. the role of innate immune pathways that drive inflammation, and 3. the central nervous system’s response to injury with a focus on the activation of spinal microglia driving painful hyperalgesic states.

  13. How effective is tetracaine 4% gel, before a peripherally inserted central catheter, in reducing procedural pain in infants: a randomized double-blind placebo controlled trial [ISRCTN75884221

    Directory of Open Access Journals (Sweden)

    Blanchard Colline

    2006-05-01

    Full Text Available Abstract Background Procedural pain relief is sub-optimal in infants, especially small and vulnerable ones. Tetracaine gel 4% (Ametop®, Smith-Nephew provides pain relief in children and larger infants, but its efficacy in smaller infants and for peripherally inserted central catheters (PICC remains uncertain. The objective of this trial was to assess the safety and efficacy of tetracaine gel on the pain response of very low birth weight (VLBW infants during insertion of a PICC. Methods Medically stable infants greater than or equal to 24 weeks gestation, requiring a non-urgent PICC, were included. Following randomization and double blinding, 1.1 g of tetracaine or placebo was applied to the skin for 30 minutes. The PICC was inserted according to a standard protocol. Pain was assessed using the Premature Infant Pain Profile (PIPP. A 3-point change in the pain score was considered clinically significant, leading to a sample size of 54 infants, with 90% statistical power. Local skin reactions and immediate adverse cardiorespiratory events were noted. The primary outcome, PIPP score at 1 minute, was analysed using an independent Student's t-test. Results Fifty-four infants were included, 27 +/- 2 weeks gestation, 916 +/- 292 grams and 6.5 +/- 3.2 days of age. Baseline characteristics were similar between groups. The mean PIPP score in the first minute was 10.88 in the treatment group as compared to 11.74 in the placebo group (difference 0.86, 95% CI -1.86, 3.58. Median duration of crying in non-intubated infants was 181 seconds in the tetracaine group compared to 68 seconds in the placebo group (difference -78, 95% CI -539, 117. Local skin erythema was observed transiently in 4 infants (3 in the treatment and 1 in the placebo group. No serious harms were observed. Conclusion Tetracaine 4% when applied for 30 minutes was not beneficial in decreasing procedural pain associated with a PICC in very small infants.

  14. Exogenous melatonin abolishes mechanical allodynia but not thermal hyperalgesia in neuropathic pain. The role of the opioid system and benzodiazepine-gabaergic mechanism.

    Science.gov (United States)

    Zurowski, D; Nowak, L; Machowska, A; Wordliczek, J; Thor, P J

    2012-12-01

    Melatonin (MT) is a neurohormone synthesized and secreted by the pineal gland. MT plays an important role in the regulation of physiological and neuroendocrine functions. The purpose of this study was to assess the overall effect of melatonin on neuropathic pain, the type of melatonin receptor involved, and potential role of the opioid system and GABA(A) receptors. The experiments were conducted by using the animal neuropathic pain model (CCI). The rats with CCI showed the characteristic for the mechanical allodynia and thermal hyperalgesia signs that were calculated by using the von Frey's and Hargreaves' tests. The conducted studies measured the effects of intraperitoneal administration of naloxone (opioid antagonist), prazosin (MT3 antagonist), luzindole (MT1/MT2 receptor antagonist), picrotoxin (GABA(A) antagonist) and flumazenil (benzodiazepine antagonist) on the antinociceptive effects caused by melatonin. Melatonin caused the increase in the pain threshold of the mechanical allodynia and the slight increase in the threshold of the thermal hyperalgesia. The pre-treatment with naloxone completely abolished the antinociceptive effects of melatonin in von Frey's test, but not thermal sensation in the Hargreaves's test. Prazosin did not have any effects, while administration of luzindole significantly suppressed the antinociceptive effect of melatonin. The antiallodynic effect of MT was also abolished by flumazenil and picrotoxin. Melatonin influences the mechanical allodynia but not thermal hyperalgesia via activation of opioid system and benzodiazepine-GABAergic pathway. Antinociceptive effects of melatonin are mostly related to the MT1/MT2 receptors interaction.

  15. Habituating pain

    DEFF Research Database (Denmark)

    Ajslev, Jeppe Zielinski Nguyen; Lund, Henrik Lambrecht; Møller, Jeppe Lykke

    2013-01-01

    In this article, we investigate the relations between discursive practices within the Danish construction industry and the perceived pain, physical deterioration, and strain affecting the construction workers. Of central importance is the widely accepted hegemonic discourse on physical strain...... and pain as unavoidable conditions in construction work. Based on 32 semi-structured interviews performed in eight case studies within four different construction professions, workers’ descriptions of physical strain and its relation to the organizational and social context are analyzed through concepts...... the industry reproduce physical strain and the habituation of pain as unquestioned conditions in construction work. The understanding of this mutual reinforcement of the necessity of physically straining, painful, high-paced construction work provides fruitful perspectives on the overrepresentation...

  16. [Mechanisms of muscle pain : significance of trigger points and tender points].

    Science.gov (United States)

    Brezinschek, H-P

    2008-12-01

    Fibromyalgia syndrome (FMS) and myofascial pain syndrome (MPS) belong to the group of chronic non-inflammatory pain syndromes affecting muscles and tendinous insertions. Important criteria in the diagnosis of both diseases are the presence of "tender points" and "trigger points". According to ACR criteria FMS is characterized by the presence of tender points whereas trigger points are typically found in MPS.The main difference is that until now tender points could only be defined in terms of their localization, whereas trigger points can be found upon palpation which may cause a specific referred pain pattern. In addition, analysis of trigger points by microdialysis demonstrated elevated levels of pro-inflammatory substances at these sites. Moreover, local treatment of trigger points either by manipulative therapy or injection appears to be most effective for prompt relief of symptoms.

  17. Elite swimmers with and without unilateral shoulder pain: mechanical hyperalgesia and active/latent muscle trigger points in neck-shoulder muscles.

    Science.gov (United States)

    Hidalgo-Lozano, A; Fernández-de-las-Peñas, C; Calderón-Soto, C; Domingo-Camara, A; Madeleine, P; Arroyo-Morales, M

    2013-02-01

    Our aim was to investigate the presence of mechanical hypersensitivity and active trigger points (TrPs) in the neck-shoulder muscles in elite swimmers with/without unilateral shoulder pain. Seventeen elite swimmers with shoulder pain; 18 swimmers without shoulder pain; and 15 elite athletes matched controls were recruited. Pressure pain thresholds (PPT) were assessed over the levator scapulae, sternocleidomastoid, upper trapezius, infraspinatus, scalene, subscapularis and tibialis anterior muscles. TrPs in the levator scapulae, upper trapezius, infraspinatus, scalene, sternocleidomastoid and subscapularis muscles were also explored. Swimmers with shoulder pain showed significant lower PPT in all muscles compared with controls (Ppain, underlining widespread mechanical hypersensitivity. The mean number of TrPs for elite swimmer with and without shoulder pain was, respectively, 4.7 ± 1 (2.1 ± 1.5 active; 2.6 ± 1.4 latent) and 4.7 ± 1.3 (1.3 ± 1.3 active; 3.4 ± 1.5 latent), whereas healthy athletes only showed latent TrPs (2.4 ± 1.2). Elite swimmers with shoulder pain showed higher number of active TrPs than swimmers without pain, whereas it was the opposite for the number of latent muscle TrP (Pmechanical hypersensitivity suggests that active TrPs play a role in the development of shoulder pain in elite swimmers.

  18. Cervical and scapulothoracic stabilization exercises with and without connective tissue massage for chronic mechanical neck pain: A prospective, randomised controlled trial.

    Science.gov (United States)

    Celenay, Seyda Toprak; Kaya, Derya Ozer; Akbayrak, Turkan

    2016-02-01

    This study was planned to assess and compare the effectiveness of cervical and scapulothoracic stabilization exercise treatment with and without connective tissue massage (CTM) on pain, anxiety, and the quality of life in patients with chronic mechanical neck pain (MNP). Sixty patients with chronic MNP (18-65 years) were recruited and randomly allocated into stabilization exercise with (Group 1, n = 30) and without the CTM (Group 2, n = 30). The program was carried out for 12 sessions, 3 days/week in 4 weeks. Pain intensity with Visual Analog Scale, pressure pain threshold with digital algometer (JTech Medical Industries, ZEVEX Company), level of anxiety with Spielberger State Trait Anxiety Inventory, and quality of life with Short Form-36 were evaluated before and after the treatment. After the program, pain intensity and the level of anxiety decrease, physical health increase in Group 1 and 2 were found (p pain threshold and mental health increase were detected in only Group 1 (p pain intensity at night, pressure pain threshold, state anxiety and mental health were seen in favor of Group 1 (p pain intensity at night, pressure pain threshold, state anxiety and mental health compared to stabilization exercise alone.

  19. The influence of a series of five dry cupping treatments on pain and mechanical thresholds in patients with chronic non-specific neck pain - a randomised controlled pilot study

    OpenAIRE

    2011-01-01

    Abstract Background In this preliminary trial we investigated the effects of dry cupping, an ancient method for treating pain syndromes, on patients with chronic non-specific neck pain. Sensory mechanical thresholds and the participants' self-reported outcome measures of pain and quality of life were evaluated. Methods Fifty patients (50.5 ± 11.9 years) were randomised to a treatment group (TG) or a waiting-list control group (WL). Patients in the TG received a series of 5 cupping treatments ...

  20. Pain. Part 2a: Trigeminal Anatomy Related to Pain.

    Science.gov (United States)

    Renton, Tara; Egbuniwe, Obi

    2015-04-01

    In order to understand the underlying principles of orofacial pain it is important to understand the corresponding anatomy and mechanisms. Paper 1 of this series explains the central nervous and peripheral nervous systems relating to pain. The trigeminal nerve is the 'great protector' of the most important region of our body. It is the largest sensory nerve of the body and over half of the sensory cortex is responsive to any stimulation within this system. This nerve is the main sensory system of the branchial arches and underpins the protection of the brain, sight, smell, airway, hearing and taste, underpinning our very existence. The brain reaction to pain within the trigeminal system has a significant and larger reaction to the threat of, and actual, pain compared with other sensory nerves. We are physiologically wired to run when threatened with pain in the trigeminal region and it is a 'miracle' that patients volunteer to sit in a dental chair and undergo dental treatment. Clinical Relevance: This paper aims to provide the dental and medical teams with a review of the trigeminal anatomy of pain and the principles of pain assessment.

  1. EFFICACY OF ACTIVE STRETCHING OVER PASSIVE STRETCHING ON THE FUNCTIONAL OUTCOME AMONG PATIENTS WITH MECHANICAL LOW BACK PAIN

    Directory of Open Access Journals (Sweden)

    Elvis Luke Fernandez

    2015-02-01

    Full Text Available Introduction: Low back pain has a significant impact on the individual’s family, socio-economic status, occupation, health system, community. Stretching is included as a part of treatment regimen for low back pain. Much controversy exists on the type of stretching technique and parameters which would prove beneficial to improve flexibility. Aim of the study was to compare the efficacy of active stretching over passive stretching, on the functional performance among patients with low back pain. Materials and method: 52 subjects with mechanical low back pains in the age group of 20-50 were enrolled for the study. Flexibility measurement and Oswestry Low Back Pain Disability Index was used as the primary outcome measure. Flexibility of Iliopsoas was measured using the modified Thomas test; Flexibility of Hamstring was measured using the active knee extension test. The subjects underwent 7 days of therapy sessions, after 7 days of therapy the individuals where re-assessed for flexibility and they were asked to fill the Oswestry Low Back Pain Disability Questionnaire. Results: 52 subjects were enrolled in the study, of which 36 subjects completed the study, among them 18 subjects in the control group and 18 subjects in intervention group. For independent groups paired t-test was used. Using the paired sample t-test significant difference was measured between the pre and post of the intervention group and control groups a significant difference of .001 was achieved in both the groups (P=.001. Discussion: The results of the present study prove that both active and passive stretching is beneficial in improving the flexibility of tight muscles in the lower limbs. Also both active stretching and passive stretching has a profound effect on the functional aspect in patients suffering with low back pain. Conclusion: The result of present study conveys that both active and passive stretch is helpful in improving the flexibility in the major muscle groups of

  2. Interactions of pannexin 1 with NMDA and P2X7 receptors in central nervous system pathologies: Possible role on chronic pain.

    Science.gov (United States)

    Bravo, D; Maturana, C J; Pelissier, T; Hernández, A; Constandil, L

    2015-11-01

    Pannexin 1 (Panx1) is a glycoprotein that acts as a membrane channel in a wide variety of tissues in mammals. In the central nervous system (CNS) Panx1 is expressed in neurons, astrocytes and microglia, participating in the pathophysiology of some CNS diseases, such as epilepsy, anoxic depolarization after stroke and neuroinflammation. In these conditions Panx1 acts as an important modulator of the neuroinflammatory response, by secreting ATP, by interacting with the P2X7 receptor (P2X7R), and as an amplifier of NMDA receptor (NMDAR) currents, particularly in conditions of pathological neuronal hyperexcitability. Here, we briefly reviewed the current evidences that support the interaction of Panx1 with NMDAR and P2X7R in pathological contexts of the CNS, with special focus in recent data supporting that Panx1 is involved in chronic pain signaling by interacting with NMDAR in neurons and with P2X7R in glia. The participation of Panx1 in chronic pain constitutes a novel topic for research in the field of clinical neurosciences and a potential target for pharmacological interventions in chronic pain.

  3. FORMATION MECHANISM AND SPATIAL PATTERN OF URBAN AGGLOMERATION IN CENTRAL JILIN OF CHINA

    Institute of Scientific and Technical Information of China (English)

    QIN Gan; ZHANG Ping-yu; JIAO Bin

    2006-01-01

    Urban agglomeration is made up of cities with different sizes to be linked by traffic network in a given area, and it is an inevitable result when urbanization reaches a certain level. Taking urban agglomerationin central Jilin(UACJ) as an example, this article analyzes the formation mechanism and spatial pattern of urban agglomeration in the less-developed area. First, the dynamics of UACJ has been analyzed from the aspects of geographical condition, economic foundation, policy background, and traffic condition. Then the development process is divided into three stages-single city, city group and city cluster. Secondly, the central cities are identified from the aspects of city centrality, and the development axes are classified based on economic communication capacity. Finally, the urban agglomeration is divided into five urban economic regions in order to establish the reasonable distribution of industries.

  4. Effects and Mechanisms of Low-Intensity Pulsed Ultrasound for Chronic Prostatitis and Chronic Pelvic Pain Syndrome.

    Science.gov (United States)

    Lin, Guiting; Reed-Maldonado, Amanda B; Lin, Maofan; Xin, Zhongcheng; Lue, Tom F

    2016-07-01

    Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is one of the most common urologic diseases, and no curative treatments have been identified. Low-intensity pulsed ultrasound (LIPUS) has been successfully used in promoting tissue healing, inhibiting inflammation and pain, differentiating stem cells, and stimulating nerve regeneration/muscle regeneration, as well as enhancing angiogenesis. Very recently, LIPUS has been proven an effective approach for CP/CPPS. This review summarizes the possible mechanisms responsible for the therapeutic effect of LIPUS for CP/CPPS. To search publications relevant to the topics of this review, the search engine for life sciences of Entrez was used. We reviewed the available evidence from 1954 through 2015 concerning LIPUS for CP/CPPS. According to the literature, both transrectal and transperineal approaches of LIPUS are effective for CP/CPPS.

  5. Effects and Mechanisms of Low-Intensity Pulsed Ultrasound for Chronic Prostatitis and Chronic Pelvic Pain Syndrome

    Directory of Open Access Journals (Sweden)

    Guiting Lin

    2016-07-01

    Full Text Available Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS is one of the most common urologic diseases, and no curative treatments have been identified. Low-intensity pulsed ultrasound (LIPUS has been successfully used in promoting tissue healing, inhibiting inflammation and pain, differentiating stem cells, and stimulating nerve regeneration/muscle regeneration, as well as enhancing angiogenesis. Very recently, LIPUS has been proven an effective approach for CP/CPPS. This review summarizes the possible mechanisms responsible for the therapeutic effect of LIPUS for CP/CPPS. To search publications relevant to the topics of this review, the search engine for life sciences of Entrez was used. We reviewed the available evidence from 1954 through 2015 concerning LIPUS for CP/CPPS. According to the literature, both transrectal and transperineal approaches of LIPUS are effective for CP/CPPS.

  6. Cost-effectiveness of minimal interventional procedures for chronic mechanical low back pain: design of four randomised controlled trials with an economic evaluation

    Directory of Open Access Journals (Sweden)

    Maas Esther T

    2012-12-01

    Full Text Available Abstract Background Minimal interventional procedures are frequently applied in patients with mechanical low back pain which is defined as pain presumably resulting from single sources: facet, disc, sacroiliac joint or a combination of these. Usually, these minimal interventional procedures are an integral part of a multidisciplinary pain programme. A recent systematic review issued by the Dutch Health Insurance Council showed that the effectiveness of these procedures for the total group of patients with chronic low back pain is yet unclear and cost-effectiveness unknown. The aim of the study is to evaluate whether a multidisciplinary pain programme with minimal interventional procedures is cost-effective compared to the multidisciplinary pain programme alone for patients with chronic mechanical low back pain who did not respond to conservative primary care and were referred to a pain clinic. Methods All patients with chronic low back pain who are referred to one of the 13 participating pain clinics will be asked to participate in an observational study. Patients with a suspected diagnosis of facet, disc or sacroiliac joint problems will receive a diagnostic block to confirm this diagnosis. If confirmed, they will be asked to participate in a Randomized Controlled Trial (RCT. For each single source a separate RCT will be conducted. Patients with a combination of facet, disc or sacroiliac joint problems will be invited for participation in a RCT as well. An economic evaluation from a societal perspective will be performed alongside these four RCTs. Patients will complete questionnaires at baseline, 3 and 6 weeks, 3, 6, 9 and 12 months after start of the treatment. Costs will be collected using self-completed cost questionnaires. Discussion No trials are yet available which have evaluated the cost-effectiveness of minimal interventional procedures in patients with chronic mechanical low back pain, which emphasizes the importance of this study

  7. Colocalization of aromatase in spinal cord astrocytes: differences in expression and relationship to mechanical and thermal hyperalgesia in murine models of a painful and a non-painful bone tumor.

    Science.gov (United States)

    O'Brien, E E; Smeester, B A; Michlitsch, K S; Lee, J-H; Beitz, A J

    2015-08-20

    While spinal cord astrocytes play a key role in the generation of cancer pain, there have been no studies that have examined the relationship of tumor-induced astrocyte activation and aromatase expression during the development of cancer pain. Here, we examined tumor-induced mechanical hyperalgesia and cold allodynia, and changes in Glial fibrillary acid protein (GFAP) and aromatase expression in murine models of painful and non-painful bone cancer. We demonstrate that implantation of fibrosarcoma cells, but not melanoma cells, produces robust mechanical hyperalgesia and cold allodynia in tumor-bearing mice compared to saline-injected controls. Secondly, this increase in mechanical hyperalgesia and cold allodynia is mirrored by significant increases in both spinal astrocyte activity and aromatase expression in the dorsal horn of fibrosarcoma-bearing mice. Importantly, we show that aromatase is only found within a subset of astrocytes and not in neurons in the lumbar spinal cord. Finally, administration of an aromatase inhibitor reduced tumor-induced hyperalgesia in fibrosarcoma-bearing animals. We conclude that a painful fibrosarcoma tumor induces a significant increase in spinal astrocyte activation and aromatase expression and that the up-regulation of aromatase plays a role in the development of bone tumor-induced hyperalgesia. Since spinal aromatase is also upregulated, but to a lesser extent, in non-painful melanoma bone tumors, it may also be neuroprotective and responsive to the changing tumor environment.

  8. Invited Commentary: Understanding Brain Mechanisms of Pain Processing in Adolescents' Non-Suicidal Self-Injury

    Science.gov (United States)

    Ballard, Elizabeth; Bosk, Abigail; Pao, Maryland

    2010-01-01

    Whereas non-suicidal self injury (NSSI) is reported in 13-23% of adolescents and is an increasingly studied topic, there has been little investigation into the pathophysiology behind self-injury. This commentary examines recent research into pain and emotional distress to discuss implications for the manner we should understand, research, and…

  9. MECHANISM OF ANALGESIC EFFECTS OF PROPOFOL ON INCISIONAL PAIN: A RAT MODEL STUDY

    Institute of Scientific and Technical Information of China (English)

    HUANG Zhi-hua; SONG Xiao-xing; HU Jiong; YU Bu-wei

    2009-01-01

    Objective To clarify the role of propofol in controlling incisional pain and its potential effects on the spinal opioid receptor expression.Methods A postoperative model of nociception was established in male Sprague-Dawley rats weighing 200-250 g. A total of 96 rats were randomly divided into 8 groups. All drugs were administered intravenously either 5min pre-operation or 5min post-operation. The analgesic effects of systemic propofol were demonstrated by the measurement of a cumulative pain score (CPS). After that, the lumbar enlargement of the spinal cord was removed to evaluate the mRNA level of the μ-opioid receptor (MOR) and δ-opioid receptor (DOR) by RT-PCR.Results CPS and DOR mRNA expressions significantly increased after the operation. Both propofol post-treatment and propofol pre-treatment groups showed significant suppression of the increased CPS and the expression of DOR mRNA evoked by pain stimulation. Interestingly, propofol pre-treatment had a more pronounced effect in decreasing CPS and the expression of DOR mRNA. Furthermore, these observations were dose-dependent. MOR mRNA expression significantly increased after operation in all animals and propofol treatment had no impact on it.Conclusion Based on these findings, we suggest that propofol can serve as a valuable adjunct in acute postoperative pain management. Systemic propofol induces an analgesic effect on acute incisional pain in a dose-dependant manner, and this effect is mediated in the spinal cord and may be associated with the spinal DOR.

  10. The pain-relieving qualities of exercise in knee osteoarthritis

    Directory of Open Access Journals (Sweden)

    Susko AM

    2013-10-01

    Full Text Available Allyn M Susko, G Kelley Fitzgerald Department of Physical Therapy, University of Pittsburgh, Pittsburgh, PA, USA Abstract: The purpose of this review article is to explore the role of therapeutic exercise in managing the pain associated with knee osteoarthritis (OA. Therapeutic exercise is often recommended as a first-line conservative treatment for knee OA, and current evidence supports exercise as an effective pain-relieving intervention. We explore the current state of evidence for exercise as a pain-relieving intervention for knee OA. Next, the mechanisms by which knee OA pain occurs and the potential ways in which exercise may act on those mechanisms are discussed. Clinical applicability and future research directions are suggested. Although evidence demonstrates that exercise reduces knee OA pain, optimal exercise mode and dosage have not been determined. In addition, it is not clearly understood whether exercise provides pain relief via peripheral or central mechanisms or a combination of both. Published clinical trials have explored a variety of interventions, but these interventions have not been specifically designed to target pain pathways. Current evidence strongly supports exercise as a pain-relieving option for those with knee OA. Future research needs to illuminate the mechanisms by which exercise reduces the pain associated with knee OA and the development of therapeutic exercise interventions to specifically target these mechanisms. Keywords: knee, OA, exercise, pain

  11. A clinical prediction rule for classifying patients with low back pain who demonstrate short-term improvement with mechanical lumbar traction

    OpenAIRE

    Cai, Congcong; Pua, Yong Hao; Lim, Kian Chong

    2009-01-01

    The objective of the study was to develop a clinical prediction rule for identifying patients with low back pain, who improved with mechanical lumbar traction. A prospective, cohort study was conducted in a physiotherapy clinic at a local hospital. Patients with low back pain, referred to physiotherapy were included in the study. The intervention was a standardized mechanical lumbar traction program, which comprised three sessions provided within 9 days. Patient demographic information, stand...

  12. Molecular mechanisms underlying the effects of statins in the central nervous system.

    Science.gov (United States)

    McFarland, Amelia J; Anoopkumar-Dukie, Shailendra; Arora, Devinder S; Grant, Gary D; McDermott, Catherine M; Perkins, Anthony V; Davey, Andrew K

    2014-11-10

    3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly referred to as statins, are widely used in the treatment of dyslipidaemia, in addition to providing primary and secondary prevention against cardiovascular disease and stroke. Statins' effects on the central nervous system (CNS), particularly on cognition and neurological disorders such as stroke and multiple sclerosis, have received increasing attention in recent years, both within the scientific community and in the media. Current understanding of statins' effects is limited by a lack of mechanism-based studies, as well as the assumption that all statins have the same pharmacological effect in the central nervous system. This review aims to provide an updated discussion on the molecular mechanisms contributing to statins' possible effects on cognitive function, neurodegenerative disease, and various neurological disorders such as stroke, epilepsy, depression and CNS cancers. Additionally, the pharmacokinetic differences between statins and how these may result in statin-specific neurological effects are also discussed.

  13. Fermilab Central Computing Facility: Energy conservation report and mechanical systems design optimization and cost analysis study

    Energy Technology Data Exchange (ETDEWEB)

    Krstulovich, S.F.

    1986-11-12

    This report is developed as part of the Fermilab Central Computing Facility Project Title II Design Documentation Update under the provisions of DOE Document 6430.1, Chapter XIII-21, Section 14, paragraph a. As such, it concentrates primarily on HVAC mechanical systems design optimization and cost analysis and should be considered as a supplement to the Title I Design Report date March 1986 wherein energy related issues are discussed pertaining to building envelope and orientation as well as electrical systems design.

  14. Body Pain Reporting in Tricare Eligible Beneficiaries with Orofacial Pain

    Science.gov (United States)

    2015-06-01

    trigeminal nociceptive neurons and maintain orofacial pain conditions. Therefore, uncontrolled pain sources at any location can significantly impact... nociceptive 6 thresholds so that non- painful stimuli are interpreted as painful . If the pathophysiology of CS persists, peripheral noxious input may no...up-regulated central nociceptive processing in patients with masticatory myofascial pain . Journal of Orofacial Pain , 18(1), 41-45. 60. Sarlani E

  15. Central Effect of Exogenous Histamine on Pain Induced by Sub-Plantar Injection of Formalin in Rabbits

    OpenAIRE

    Esmaeal Tamaddonfard

    2010-01-01

    In the present study, the effects of intracerebroventricular (ICV) administration of normal saline (control), histamine, mepyramine (a histamine H1-receptor antagonist) and ranitidine (a histamine H2-receptor antagonist) were investigated on the formalin-induced pain in rabbits. Subcutaneous (SC) injection of a formalin (100 μl, 5%) solution into the ventral surface of the right hind paw was performed, and the time durations spent licking and biting the injected paw were measured in 10 min bl...

  16. An increased response to experimental muscle pain is related to psychological status in women with chronic non-traumatic neck-shoulder pain

    Directory of Open Access Journals (Sweden)

    Persson Ann L

    2011-10-01

    Full Text Available Abstract Background Neck-shoulder pain conditions, e.g., chronic trapezius myalgia, have been associated with sensory disturbances such as increased sensitivity to experimentally induced pain. This study investigated pain sensitivity in terms of bilateral pressure pain thresholds over the trapezius and tibialis anterior muscles and pain responses after a unilateral hypertonic saline infusion into the right legs tibialis anterior muscle and related those parameters to intensity and area size of the clinical pain and to psychological factors (sleeping problems, depression, anxiety, catastrophizing and fear-avoidance. Methods Nineteen women with chronic non-traumatic neck-shoulder pain but without simultaneous anatomically widespread clinical pain (NSP and 30 age-matched pain-free female control subjects (CON participated in the study. Results NSP had lower pressure pain thresholds over the trapezius and over the tibialis anterior muscles and experienced hypertonic saline-evoked pain in the tibialis anterior muscle to be significantly more intense and locally more widespread than CON. More intense symptoms of anxiety and depression together with a higher disability level were associated with increased pain responses to experimental pain induction and a larger area size of the clinical neck-shoulder pain at its worst. Conclusion These results indicate that central mechanisms e.g., central sensitization and altered descending control, are involved in chronic neck-shoulder pain since sensory hypersensitivity was found in areas distant to the site of clinical pain. Psychological status was found to interact with the perception, intensity, duration and distribution of induced pain (hypertonic saline together with the spreading of clinical pain. The duration and intensity of pain correlated negatively with pressure pain thresholds.

  17. Neurophysiological characterization of postherniotomy pain

    DEFF Research Database (Denmark)

    Aasvang, Eske Kvanner; Brandsborg, B.; Christensen, B.

    2008-01-01

    pain on the painful side than on the unaffected side in pain patients, and was not observed in controls. Our findings showed large and small fiber dysfunction in both pain and pain-free patients but more profound in pain patients and with signs of central sensitization (abnormal temporal summation......). The specific finding of reduced pain detection threshold over the external inguinal annulus is consistent with damage to the cutaneous innervation territory of nervous structures in the inguinal region. The correspondence between pain location and sensory disturbance suggests that the pain is neuropathic...

  18. Neck pain

    OpenAIRE

    2002-01-01

    Non-specific neck pain has a postural or mechanical basis, and affects about two thirds of people at some stage, especially in middle age. Acute neck pain resolves within days or weeks, but becomes chronic in about 10% of people.Whiplash injuries follow sudden acceleration–deceleration of the neck, such as in road traffic or sporting accidents. Up to 40% of people continue to report symptoms 15 years after the accident.

  19. The Brief Illness Perceptions Questionnaire identifies 3 classes of people seeking rehabilitation for mechanical neck pain.

    Science.gov (United States)

    Walton, David M; Lefebvre, Andy; Reynolds, Darcy

    2015-06-01

    Illness representations pertain to the ways in which an individual constructs and understands the experience of a health condition. The Brief Illness Perceptions Questionnaire (BIPQ) comprises 9 items intended to capture the key components of the Illness Representations Model. The purpose of this paper was to explore the utility of the BIPQ for evaluating and classifying uncomplicated mechanical neck pain in the rehabilitation setting. A convenience sample of 198 subjects presenting to physiotherapy for neck pain problems were used in this study. In the first step, 183 subjects completed the BIPQ and a series of related cognitive measures. Latent class analysis (LCA) was used to explore the number of identifiable classes amongst the sample based on BIPQ response patterns. A regression equation was created to facilitate classification. In the second step, an independent sample of 15 subjects were classified using the equation established in step 1, and they were followed over a 3 month period. The LCA revealed 3 classes of subjects with optimal fit statistics: mildly affected, moderately affected, and severely affected. Inter-group comparisons of the secondary cognitive measures supported these labels. Classification accuracy of a regression equation was high (94.5%). Applying the equation to the independent longitudinal sample revealed that it functioned equally well and that the classes may have prognostic value. The BIPQ may be a useful clinical tool for classification of neck pain.

  20. Mechanism of relation among heart meridian, referred cardiac pain and heart

    Institute of Scientific and Technical Information of China (English)

    RONG; Peijing(荣培晶); ZHU; Bing(朱兵)

    2002-01-01

    It has been demonstrated that an important clinical phenomenon often associated with visceral diseases is the referred pain to somatic structures, especially to the body areaof homo-segmental innervation. It is interesting that the somatic foci of cardiac referred pain wereoften and mainly distributed along the heart meridian (HM), whereas the acupoints of HM havebeen applied to treat cardiac disease since ancient times. The purpose of this study was to inves-tigate the neural relationship between the cardiac referred pain and the heart meridian.Fluorescent triple-labeling was injected into the pericardium, some acupoints of HM and lung me-ridian (LM, for control). The responses of the left cardiac sympathetic nerve and of the EMG in left HM and LM were electrophysiologically studied, when the electrical stimuli were applied to the acupoints of left HM and to the left cardiac sympathetic nerve. More double-labeled neurons in HM-heart, not in LM-heart, were observed in the ipsilateral dorsal root ganglia of the spinal segments C8-T3. Electric stimulation of the acupoints of left HM was able to elicit more responses of left cardiac sympathetic nerve than that of the LM-acupoints. Electric stimulation of the left cardiac sympathetic nerve resulted in stronger activities of EMG-response in the acupoints of left HM than in LM-acupoints. We conclude that double-labeling study has provided direct evidence for the existence of dichotomizing afferent fibers that supply both the pericardium and HM. Electrophysiological results show that HM is more closely related functionally to heart. These findings provide a possible morphological and physiological explanation for the referred cardiac pain and HM-heart interrelation.

  1. Neonatal pain.

    Science.gov (United States)

    Walker, Suellen M

    2014-01-01

    Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback.

  2. TAFA4, a Chemokine-like Protein, Modulates Injury-Induced Mechanical and Chemical Pain Hypersensitivity in Mice

    Directory of Open Access Journals (Sweden)

    Marie-Claire Delfini

    2013-10-01

    Full Text Available C-low-threshold mechanoreceptors (C-LTMRs are unique among C-unmyelinated primary sensory neurons. These neurons convey two opposite aspects of touch sensation: a sensation of pleasantness, and a sensation of injury-induced mechanical pain. Here, we show that TAFA4 is a specific marker of C-LTMRs. Genetic labeling in combination with electrophysiological recordings show that TAFA4+ neurons have intrinsic properties of mechano-nociceptors. TAFA4-null mice exhibit enhanced mechanical and chemical hypersensitivity following inflammation and nerve injury as well as increased excitability of spinal cord lamina IIi neurons, which could be reversed by intrathecal or bath application of recombinant TAFA4 protein. In wild-type C57/Bl6 mice, intrathecal administration of TAFA4 strongly reversed carrageenan-induced mechanical hypersensitivity, suggesting a potent analgesic role of TAFA4 in pain relief. Our data provide insights into how C-LTMR-derived TAFA4 modulates neuronal excitability and controls the threshold of somatic sensation.

  3. TAFA4, a chemokine-like protein, modulates injury-induced mechanical and chemical pain hypersensitivity in mice.

    Science.gov (United States)

    Delfini, Marie-Claire; Mantilleri, Annabelle; Gaillard, Stéphane; Hao, Jizhe; Reynders, Ana; Malapert, Pascale; Alonso, Serge; François, Amaury; Barrere, Christian; Seal, Rebecca; Landry, Marc; Eschallier, Alain; Alloui, Abdelkrim; Bourinet, Emmanuel; Delmas, Patrick; Le Feuvre, Yves; Moqrich, Aziz

    2013-10-31

    C-low-threshold mechanoreceptors (C-LTMRs) are unique among C-unmyelinated primary sensory neurons. These neurons convey two opposite aspects of touch sensation: a sensation of pleasantness, and a sensation of injury-induced mechanical pain. Here, we show that TAFA4 is a specific marker of C-LTMRs. Genetic labeling in combination with electrophysiological recordings show that TAFA4+ neurons have intrinsic properties of mechano-nociceptors. TAFA4-null mice exhibit enhanced mechanical and chemical hypersensitivity following inflammation and nerve injury as well as increased excitability of spinal cord lamina IIi neurons, which could be reversed by intrathecal or bath application of recombinant TAFA4 protein. In wild-type C57/Bl6 mice, intrathecal administration of TAFA4 strongly reversed carrageenan-induced mechanical hypersensitivity, suggesting a potent analgesic role of TAFA4 in pain relief. Our data provide insights into how C-LTMR-derived TAFA4 modulates neuronal excitability and controls the threshold of somatic sensation.

  4. Cognitive-behavioral mechanisms in a pain-avoidance and a pain-persistence treatment for high-risk fibromyalgia patients

    NARCIS (Netherlands)

    Koulil, S. van; Kraaimaat, F.W.; Lankveld, W.G.J.M. van; Helmond, T. van; Vedder, A.; Hoorn, H. van; Donders, A.R.T.; Thieme, K.; Cats, H.; Riel, P.L. van; Evers, A.W.M.

    2011-01-01

    OBJECTIVE: The heterogeneity of cognitive-behavioral patterns in patients with fibromyalgia (FM) has been proposed to underlie the variability in treatment outcomes. It has previously been shown that pain-avoidance and pain-persistence treatments tailored to the patient's pattern are effective in im

  5. Chronic pain after hysterectomy

    DEFF Research Database (Denmark)

    Brandsborg, B.; Nikolajsen, L.; Kehlet, H.;

    2008-01-01

    BACKGROUND: Chronic pain is a well-known adverse effect of surgery, but the risk of chronic pain after gynaecological surgery is less established. METHOD: This review summarizes studies on chronic pain following hysterectomy. The underlying mechanisms and risk factors for the development of chronic...... post-hysterectomy pain are discussed. RESULTS AND CONCLUSION: Chronic pain is reported by 5-32% of women after hysterectomy. A guideline is proposed for future prospective studies Udgivelsesdato: 2008/3...

  6. Chronic pain after hysterectomy

    DEFF Research Database (Denmark)

    Brandsborg, B; Nikolajsen, L; Kehlet, Henrik;

    2008-01-01

    BACKGROUND: Chronic pain is a well-known adverse effect of surgery, but the risk of chronic pain after gynaecological surgery is less established. METHOD: This review summarizes studies on chronic pain following hysterectomy. The underlying mechanisms and risk factors for the development of chronic...... post-hysterectomy pain are discussed. RESULTS AND CONCLUSION: Chronic pain is reported by 5-32% of women after hysterectomy. A guideline is proposed for future prospective studies. Udgivelsesdato: 2008-Mar...

  7. Isometric knee extensor fatigue following a Wingate test: peripheral and central mechanisms.

    Science.gov (United States)

    Fernandez-del-Olmo, M; Rodriguez, F A; Marquez, G; Iglesias, X; Marina, M; Benitez, A; Vallejo, L; Acero, R M

    2013-02-01

    Central and peripheral fatigue have been explored during and after running or cycling exercises. However, the fatigue mechanisms associated with a short maximal cycling exercise (30 s Wingate test) have not been investigated. In this study, 10 volunteer subjects performed several isometric voluntary contractions using the leg muscle extensors before and after two bouts of cycling at 25% of maximal power output and two bouts of Wingate tests. Transcranial magnetic stimulation (TMS) and electrical motor nerve stimulation (NM) were applied at rest and during the voluntary contractions. Maximal voluntary contraction (MVC), voluntary activation (VA), twitch amplitude evoked by electrical nerve stimulation, M wave and motor potential evoked by TMS (MEP) were recorded. MVC, VA and twitch amplitude evoked at rest by NM decreased significantly after the first and second Wingate tests, indicating central and peripheral fatigue. MVC and VA, but not the twitch amplitude evoked by NM, recovered before the second Wingate test. These results suggest that the Wingate test results in a decrease in MVC associated with peripheral and central fatigue. While the peripheral fatigue is associated with an intramuscular impairment, the central fatigue seems to be the main reason for the Wingate test-induced impairment of MVC.

  8. Umbilical cord blood stem cells treatment for central pain: one case report%异体脐带血干细胞治疗中枢性疼痛一例

    Institute of Scientific and Technical Information of China (English)

    岳宝玲; 范亚林; 李香社; 郑丽; 侯会荣; 高丽昕

    2012-01-01

    Objective To study the effective of stem cell transplantation in a central pain patient. Methods There was a central pain case who had suffered central pain which resulted in brain ischemia-hypoxia. The patient was given 6 packets of umbilical cord blood stem cells transplantation ( 2 intravenous injection and 4 lumber puncture ). She was received stem cell treatment every 5 days. We observed the condition of central pain for 2 months. Result There was some improvement of pain and life quality from the 2rd stem cells transplantation. But patient felt pain after the 2rd month. Conclusion Umbilical cord blood stem cell transplantation was a new treatment method for central pain.%目的 探讨1例中枢性疼痛患者接受脐带血干细胞移植后症状转归.方法 随访我院1例脑缺血缺氧后中枢性疼痛患者给予2次静脉、4次腰穿鞘内注射途径移植干细胞,每次移植间隔5天,治疗后随访患者疼痛变化情况2个月.结果 从第2次脐带血干细胞移植开始,患者的疼痛情况及生活质量均有一定改善,移植结束后2个月患者疼痛又开始反复.结论 脐带血干细胞移植可能为中枢性疼痛的治疗提供新的治疗途径.

  9. Pain Disorder

    Directory of Open Access Journals (Sweden)

    Carlos Capela

    2014-06-01

    Full Text Available Pain disorder is a psychiatric disorder diagnosed when the pain becomes the predominant focus of the clinical presentation and causes significant distress or impairment. Besides the high economic impact, there is a reciprocal relationship with the affective state. Pain is a subjective sensation and its severity and quality of experience in an individual is dependent on a complex mix of factors. In the treatment of acute pain, the primary purpose is pain relief, while chronic pain typically requires a combination of psychotropic drugs. In this context, it is also important to recognize and treat depression. Psychological treatments aimed at providing mechanisms to allow patients to "control and live with the pain" rather than aspire to eliminate it completely. A growing group of researchers proposes the elimination of the chapter of Somatoform Disorders and the modification of the category "psychological factors affecting a medical condition" to "psychological factors affecting an identified or feared medical condition" with clinical entities as ubchapters, largely based upon Diagnostics for Psychosomatic Research criteria.

  10. Chronic widespread pain in spondyloarthritis

    Directory of Open Access Journals (Sweden)

    F. Atzeni

    2014-06-01

    Full Text Available The pain associated with spondyloarthritis (SpA can be intense, persistent and disabling. It frequently has a multifactorial, simultaneously central and peripheral origin, and may be due to currently active inflammation, or joint damage and tissue destruction arising from a previous inflammatory condition. Inflammatory pain symptoms can be reduced by non-steroidal anti-inflammatory drugs, but many patients continue to experience moderate pain due to alterations in the mechanisms that regulate central pain, as in the case of the chronic widespread pain (CWP that characterises fibromyalgia (FM. The importance of distinguishing SpA and FM is underlined by the fact that SpA is currently treated with costly drugs such as tumour necrosis factor (TNF inhibitors, and direct costs are higher in patients with concomitant CWP or FM than in those with FM or SpA alone. Optimal treatment needs to take into account symptoms such as fatigue, mood, sleep, and the overall quality of life, and is based on the use of tricyclic antidepressants or selective serotonin reuptake inhibitors such as fluoxetine, rather than adjustments in the dose of anti-TNF agents or disease-modifying drugs.

  11. Pain, emotion, headache.

    Science.gov (United States)

    Bussone, Gennaro; Grazzi, Licia; Panerai, Alberto E

    2012-10-01

    Pain has been considered as part of a defensive strategy whose specific role is to signal an immediate active danger to the organism. This definition fits well for acute pain. It does not work well, however, for chronic pain that is maintained even in absence of an ongoing, active threat. Currently, acute and chronic pain are considered to be separate conditions. What follows is a review of the different theories about pain and its history. Different hypotheses regarding pain mechanisms are illustrated. New data emerging from scientific research on chronic pain (migraine in particular) involving innovative imaging techniques are reported and discussed.

  12. Mechanisms regulating the development of oligodendrocytes and central nervous system myelin.

    Science.gov (United States)

    Mitew, S; Hay, C M; Peckham, H; Xiao, J; Koenning, M; Emery, B

    2014-09-12

    Oligodendrocytes and the myelin they produce are a remarkable vertebrate specialization that enables rapid and efficient nerve conduction within the central nervous system. The generation of myelin during development involves a finely-tuned pathway of oligodendrocyte precursor specification, proliferation and migration followed by differentiation and the subsequent myelination of appropriate axons. In this review we summarize the molecular mechanisms known to regulate each of these processes, including the extracellular ligands that promote or inhibit development of the oligodendrocyte lineage, the intracellular pathways they signal through and the key transcription factors that mediate their effects. Many of these regulatory mechanisms have recurring roles in regulating several transitions during oligodendrocyte development, highlighting their importance. It is also highly likely that many of these developmental mechanisms will also be involved in myelin repair in human neurological disease.

  13. Gamma oscillations as a neuronal correlate of the attentional effects of pain.

    Science.gov (United States)

    Tiemann, Laura; Schulz, Enrico; Gross, Joachim; Ploner, Markus

    2010-08-01

    Successful behavior requires the attentional selection and preferred processing of behaviorally relevant sensory information. Painful stimuli are of utmost behavioral relevance and can therefore involuntarily affect attentional resources and interfere with ongoing behavior. However, the neuronal mechanisms which subserve the involuntary attentional effects of pain are largely unknown yet. Here, we therefore investigated the neuronal mechanisms of the attentional effects of pain by using electroencephalography during a visual attention task with the concurrent presentation of painful stimuli. Our results confirm that painful and visual stimuli induce gamma oscillations over central and occipital areas, respectively. Pain-induced gamma oscillations were correlated with pain-induced changes in visual gamma oscillations. Behaviorally, we observed variable effects of pain on visual reaction times, yielding an increase of reaction times for some subjects, as well as a decrease of reaction times for others. Most importantly, however, these changes in visual task performance were significantly related to pain-induced changes of visual gamma oscillations. These findings demonstrate that the variable attentional effects of pain are closely related to changes in neuronal gamma oscillations in the human brain. In the hypervigilant state of chronic pain, maladaptive changes in the attentional effects of pain may be associated with abnormal changes in neuronal gamma oscillations. Our findings may thus contribute to the understanding of the neuronal substrates of pain in health and may open a new window towards the understanding of pathological alterations of the pain experience in chronic pain syndromes.

  14. The pain interactome: connecting pain-specific protein interactions.

    Science.gov (United States)

    Jamieson, Daniel G; Moss, Andrew; Kennedy, Michael; Jones, Sherrie; Nenadic, Goran; Robertson, David L; Sidders, Ben

    2014-11-01

    Understanding the molecular mechanisms associated with disease is a central goal of modern medical research. As such, many thousands of experiments have been published that detail individual molecular events that contribute to a disease. Here we use a semi-automated text mining approach to accurately and exhaustively curate the primary literature for chronic pain states. In so doing, we create a comprehensive network of 1,002 contextualized protein-protein interactions (PPIs) specifically associated with pain. The PPIs form a highly interconnected and coherent structure, and the resulting network provides an alternative to those derived from connecting genes associated with pain using interactions that have not been shown to occur in a painful state. We exploit the contextual data associated with our interactions to analyse subnetworks specific to inflammatory and neuropathic pain, and to various anatomical regions. Here, we identify potential targets for further study and several drug-repurposing opportunities. Finally, the network provides a framework for the interpretation of new data within the field of pain.

  15. Fetal pain.

    Science.gov (United States)

    Rokyta, Richard

    2008-12-01

    The fetus reacts to nociceptive stimulations through different motor, autonomic, vegetative, hormonal, and metabolic changes relatively early in the gestation period. With respect to the fact that the modulatory system does not yet exist, the first reactions are purely reflexive and without connection to the type of stimulus. While the fetal nervous system is able to react through protective reflexes to potentially harmful stimuli, there is no accurate evidence concerning pain sensations in this early period. Cortical processes occur only after thalamocortical connections and pathways have been completed at the 26th gestational week. Harmful (painful) stimuli, especially in fetuses have an adverse effect on the development of humans regardless of the processes in brain. Moreover, pain activates a number of subcortical mechanisms and a wide spectrum of stress responses influence the maturation of thalamocortical pathways and other cortical activation which are very important in pain processing.

  16. Involvement of peripheral artemin signaling in tongue pain: possible mechanism in burning mouth syndrome.

    Science.gov (United States)

    Shinoda, Masamichi; Takeda, Mamoru; Honda, Kuniya; Maruno, Mitsuru; Katagiri, Ayano; Satoh-Kuriwada, Shizuko; Shoji, Noriaki; Tsuchiya, Masahiro; Iwata, Koichi

    2015-12-01

    Burning mouth syndrome is characterized by altered sensory qualities, namely tongue pain hypersensitivity. We found that the mRNA expression of Artemin (Artn) in the tongue mucosa of patients with burning mouth syndrome was significantly higher than that of control subjects, and we developed a mouse model of burning mouth syndrome by application of 2,4,6-trinitrobenzene sulfonic acid (TNBS) diluted with 50% ethanol to the dorsum of the tongue. TNBS treatment to the tongue induced persistent, week-long, noninflammatory tongue pain and a significant increase in Artn expression in the tongue mucosa and marked tongue heat hyperalgesia. Following TNBS treatment, the successive administration of the transient receptor potential vanilloid 1 (TRPV1) antagonist SB366791 or neutralizing anti-Artn antibody completely inhibited the heat hyperalgesia. The number of glial cell line-derived neurotrophic factor family receptor α3 (GFRα3)-positive and TRPV1-positive trigeminal ganglion (TG) neurons innervating the tongue significantly increased following TNBS treatment and was significantly reduced by successive administration of neutralizing anti-Artn antibody. The capsaicin-induced current in TG neurons innervating the tongue was enhanced following TNBS treatment and was inhibited by local administration of neutralizing anti-Artn antibody to the tongue. These results suggest that the overexpression of Artn in the TNBS-treated tongue increases the membrane excitability of TG neurons innervating the tongue by increasing TRPV1 sensitivity, which causes heat hyperalgesia. This model may be useful for the study of tongue pain hypersensitivity associated with burning mouth syndrome.

  17. Perspectives in Pancreatic Pain

    Directory of Open Access Journals (Sweden)

    A. S. Salim

    1997-01-01

    Full Text Available This review describes some of the mechanisms which are thought to be important in the causation of pain in chronic pancreatitis. Both medical and surgical techniques for treating this pain are described.

  18. [The phenomenon of pain in the history of music – observations of neurobiological mechanisms of pain and its expressions in western music].

    Science.gov (United States)

    Gasenzer, E R; Neugebauer, E A M

    2014-12-01

    Purpose of this essay is to provide a historical overview how music has dealt with the emotion and sensation of pain, as well as an overview over the more recent medical research into the relationship of music and pain. Since the beginnings of western music humans have put their emotions into musical sounds. During the baroque era, composers developed musical styles that expressed human emotions and our experiences of nature. In some compositions, like in operas, we find musical representations of pain. During Romanticism artists began to intrude into the soul of their audience. New expressive harmonies and styles touch the soul and the consciousness of the listener. With the inception of atonality dissonant sounds where experienced as a physical pain.The physiology of deep brain structures (like thalamus, hypothalamus or limbic system) and the physiology of the acoustic pathway process consonant and dissonant sound and musical perceptions in ways, that are similar to the perception of pain. In the thalamus and in the limbic system music and pain meet.The relationships of music and pain is a wide open research field with such interesting questions as the role of dopamine in the perception of consonant or dissonant music, or the processing of pain during music listening. Musicology has not yet embarked on a general investigation of how musical compositions express pain and how that has developed or changed over the centuries. Music therapy, neuro-musicology and the performing arts medicine are scientific fields that offer a lot of ideas for medical and musical research projects.

  19. Investigation of centrally and peripherally acting analgesic and anti inflammatory activity of biological immune response modulator (an Amazonian plant extract in animal models of pain and inflammation

    Directory of Open Access Journals (Sweden)

    Mital Ravalji

    2015-04-01

    Conclusion: Our study results show that BIRM has the potential anti-inflammatory property and is able to exert its anti-nociceptive effect through both central and peripheral mechanisms. [Int J Basic Clin Pharmacol 2015; 4(2.000: 342-348

  20. A modern neuroscience approach to chronic spinal pain: combining pain neuroscience education with cognition-targeted motor control training.

    Science.gov (United States)

    Nijs, Jo; Meeus, Mira; Cagnie, Barbara; Roussel, Nathalie A; Dolphens, Mieke; Van Oosterwijck, Jessica; Danneels, Lieven

    2014-05-01

    Chronic spinal pain (CSP) is a severely disabling disorder, including nontraumatic chronic low back and neck pain, failed back surgery, and chronic whiplash-associated disorders. Much of the current therapy is focused on input mechanisms (treating peripheral elements such as muscles and joints) and output mechanisms (addressing motor control), while there is less attention to processing (central) mechanisms. In addition to the compelling evidence for impaired motor control of spinal muscles in patients with CSP, there is increasing evidence that central mechanisms (ie, hyperexcitability of the central nervous system and brain abnormalities) play a role in CSP. Hence, treatments for CSP should address not only peripheral dysfunctions but also the brain. Therefore, a modern neuroscience approach, comprising therapeutic pain neuroscience education followed by cognition-targeted motor control training, is proposed. This perspective article explains why and how such an approach to CSP can be applied in physical therapist practice.