Peripheral Pain Generators Research Articles

Image-guided peripheral nerve interventions- applications and techniques

Interventional radiology continues to be at the forefront of acute and chronic pain management. Our unique imaging expertise and ability to target difficult to reach structures allows for the continuous development of new ways to treat a variety of pain generators. In addition, the advent of thermal ablation techniques and technologies has provided a unique opportunity to offer patients more durable and predictable options to treat their pain. This is particularly important during the opioid epidemic, as multiple local and international governmental bodies push for physicians to create ways to manage pain while reducing the need for long-term opioid dependence. This article aims to review various image-guided techniques and tools for the treatment of pain related to peripheral pain generators, with a focus on the extremities, lumbosacral and pelvic region, and the chest wall. For each target and pathology, we will discuss general etiology, anatomy, procedural approach, and briefly evaluate the supporting literature in each clinical situation.

A Practical Guide to Sigma-1 Receptor Positron Emission Tomography/Magnetic Resonance Imaging: A New Clinical Molecular Imaging Method to Identify Peripheral Pain Generators in Patients with Chronic Pain.

Accurately identifying the peripheral pain generator in patients with chronic pain remains a major challenge for modern medicine. Millions of patients around the world suffer endlessly from difficult-to-manage debilitating pain because of very limited diagnostic tests and a paucity of pain therapies. To help these patients, we have developed a novel clinical molecular imaging approach, and, in its early stages, it has been shown to accurately identify the exact site of pain generation using an imaging biomarker for the sigma-1 receptor and positron emission tomography/magnetic resonance imaging. We hope the description of the work in this article can help others begin their own pain imaging programs at their respective institutions.

Can Central Sensitization After Injury Persist as an Autonomous Pain Generator? A Comprehensive Search for Evidence.

To conduct a comprehensive search for evidence with regard to whether central sensitization after an injury can act as a persistent autonomous pain generator after the inducing injury has healed. We searched Medline on PubMed and the Cochrane Library, screening 3,572 abstracts, from which 937 full-text articles were obtained, with 186 of these discarded as irrelevant to the question being posed. The remaining 751 articles were studied for evidence. Fourteen publications were judged to provide weak evidence for the hypothesis of central sensitization as a persisting autonomous pain generator, but none addressed the question directly. No strong evidence for the affirmative answer was found. Sixty-one publications were judged to provide weak evidence for a negative answer, and ten were judged to provide strong evidence. Unexpectedly, serious weaknesses were discovered in the literature underpinning the validity of the clinical diagnosis of central sensitization in humans: 1) inappropriate extrapolation, in many publications, of laboratory animal data to humans; 2) failure to demonstrate the absence of peripheral pain generators that might be perpetuating central sensitization; and 3) many factors now shown to confound what is being measured by quantitative sensory testing, conditioned pain modulation, and the Central Sensitization Inventory. We found no evidence proving that central sensitization can persist as an autonomous pain generator after the initiating injury has healed. Our review has also shown that the evidential basis for the diagnosis of central sensitization in individual patients is seriously in question.

Identifying Musculoskeletal Pain Generators Using Clinical PET.

Identifying the source of a person's pain is a significant clinical challenge because the physical sensation of pain is believed to be subjective and difficult to quantify. The experience of pain is not only modulated by the individual's threshold to painful stimuli but also a product of the person's affective contributions, such as fear, anxiety, and previous experiences. Perhaps then to quantify pain is to examine the degree of nociception and pro-nociceptive inflammation, that is, the extent of cellular, chemical, and molecular changes that occur in pain-generating processes. Measuring changes in the local density of receptors, ion channels, mediators, and inflammatory/immune cells that are involved in the painful phenotype using targeted, highly sensitive, and specific positron emission tomography (PET) radiotracers is therefore a promising approach toward objectively identifying peripheral pain generators. Although several preclinical radiotracer candidates are being developed, a growing number of ongoing clinical PET imaging approaches can measure the degree of target concentration and thus serve as a readout for sites of pain generation. Further, when PET is combined with the spatial and contrast resolution afforded by magnetic resonance imaging, nuclear medicine physicians and radiologists can potentially identify pain drivers with greater accuracy and confidence. Clinical PET imaging approaches with fluorine-18 fluorodeoxyglucose, fluorine-18 sodium fluoride, and sigma-1 receptor PET radioligand and translocator protein radioligands to isolate the source of pain are described here.

Euphorbia bicolor (Euphorbiaceae) Latex Phytochemicals Induce Long-Lasting Non-Opioid Peripheral Analgesia in a Rat Model of Inflammatory Pain.

The negative side effects of opioid-based narcotics underscore the search for alternative non-opioid bioactive compounds that act on the peripheral nervous system to avoid central nervous system-mediated side effects. The transient receptor potential V1 ion channel (TRPV1) is a peripheral pain generator activated and sensitized by heat, capsaicin, and a variety of endogenous ligands. TRPV1 contributes to peripheral sensitization and hyperalgesia, in part, via triggering the release of proinflammatory peptides, such as calcitonin gene-related peptide (CGRP), both locally and at the dorsal horn of the spinal cord. Ultrapotent exogenous TRPV1 agonists, such as resiniferatoxin identified in the latex of the exotic Euphorbia resinifera, trigger hyperalgesia followed by long lasting, peripheral analgesia. The present study reports on the analgesic properties of Euphorbia bicolor, a relative of E. resinifera, native to the Southern United States. The study hypothesized that E. bicolor latex extract induces long-lasting, non-opioid peripheral analgesia in a rat model of inflammatory pain. Both inflamed and non-inflamed adult male and female rats were injected with the methanolic extract of E. bicolor latex into the hindpaw and changes in pain behaviors were reassessed at various time points up to 4 weeks. Primary sensory neuron cultures also were treated with the latex extract or vehicle for 15 min followed by stimulation with the TRPV1 agonist capsaicin. Results showed that E. bicolor latex extract evoked significant pain behaviors in both male and female rats at 20 min post-injection and lasting around 1–2 h. At 6 h post-injection, analgesia was observed in male rats that lasted up to 4 weeks, whereas in females the onset of analgesia was delayed to 72 h post-injection. In sensory neurons, latex extract significantly reduced capsaicin-evoked CGRP release. Blocking TRPV1, but not opioid receptors, attenuated the onset of analgesia and capsaicin-induced CGRP release. Latex was analyzed by mass spectrometry and eleven candidate compounds were identified and reported here. These findings indicate that phytochemicals in the E. bicolor latex induce hyperalgesia followed by peripheral, non-opioid analgesia in both male and female rats, which occurs in part via TRPV1 and may provide novel, non-opioid peripheral analgesics that warrant further examination.

Myofascial pain syndrome and trigger points: evaluation and treatment in patients with musculoskeletal pain.

Myofascial pain syndrome is a chronic pain condition characterized by the presence of myofascial trigger point, a hyperirritable painful spot involving a limited number of muscle fibers. The literature suggest that myofascial trigger points should be considered peripheral pain generators and this critical review will summarize recent findings concerning the clinical evaluation and the treatment of myofascial trigger points. The clinical features of myofascial trigger points and their contribution to the patient pain and disability have been detailed in several recent studies, which support the clinical relevance of the condition. Recent studies reported that manual palpation to identify MTrPs has good reliability, although some limitations are intrinsic to the diagnostic criteria. During the last decade, a plethora of treatments have been proposed and positive effects on pain and function demonstrated. The myofascial trigger point phenomenon has good face validity and is clinically relevant. Clinicians are encouraged to consider the contribution of myofascial trigger points to the patient's pain and disability through a careful medical history and a specific manual examination. Patients with myofascial trigger points will benefit from a multimodal treatment plan including dry needling and manual therapy techniques. Internal and external validity of research within the field must be improved.

Spasmophilia and entrapment nerve syndrome comorbidities in fibromyalgic patients: a possible neuromuscular pain generator.

This paper is aimed at investigating whether peripheral dysfunction at the neuromuscular level may represent a pain generator in fibromyalgia. We studied the prevalence of spasmophilia (SP), carpal tunnel syndrome (CTS) and ulnar neuropathy at the elbow (UNE) in a group of 40 subjects suffering from fibromyalgia. Clinical and electrophysiological data were obtained to ascertain whether comorbid conditions were present. For subjective evaluation of symptoms severity, validated questionnaires for CTS and UNE were completed by patients. Twenty subjects were positive for SP (50%); CTS was diagnosed in 12 subjects (30%); no patient suffered from UNE; 6 subjects were affected at the same time by SP and CTS (15%); 14 subjects (35%) were affected by SP alone. The prevalence of CTS and SP was higher in fibromyalgia subjects than in the general population. The scores of the questionnaires related to CTS were significantly higher in fibromyalgia subjects positive for CTS, with respect to the other subjects. In fibromyalgia, CTS and SP may be considered clinical entities in themselves, the importance of which lies in their acting as peripheral pain generators that enhance or initiate central sensitization, thereby contributing to chronic widespread pain. The amplification of pain is indeed a correctable/misguided message that occurs inside the brain of fibromyalgia subjects and identification and local treatment of pain generators would lessen the total pain burden. The magnitude of the overlap in symptoms between fibromyalgia and CTS/SP necessitates careful investigation of these conditions.

Biopsychosocial Profiles and Functional Correlates in Older Adults with Chronic Low Back Pain: A Preliminary Study

To describe key peripheral and central nervous system (CNS) conditions in a group of older adults with chronic low back pain (CLBP) and their association with pain severity and self-reported and performance-based physical function. Cross-sectional. Outpatient VA clinics. Forty-seven community-dwelling veterans with CLBP (age 68.0 ± 6.5 years, range = 60-88 years, 12.8% female, 66% white) participated. Data were collected on peripheral pain generators-body mass index, American College of Rheumatology hip osteoarthritis criteria, neurogenic claudication (i.e., spinal stenosis), sacroiliac joint (SIJ) pain, myofascial pain, leg length discrepancy (LLD), and iliotibial band pain; and CNS pain generators-anxiety (GAD-7), depression (PHQ-9), insomnia (Insomnia Severity Index), maladaptive coping (Fear Avoidance Beliefs Questionnaire, Cognitive Strategies Questionnaire), and fibromyalgia (fibromyalgia survey). Outcomes were pain severity (0 to 10 scale, seven-day average and worst), self-reported pain interference (Roland Morris [RM] questionnaire), and gait speed. Approximately 96% had at least one peripheral CLBP contributor, 83% had at least one CNS contributor, and 80.9% had both peripheral and CNS contributors. Of the peripheral conditions, only SIJ pain and LLD were associated with outcomes. All of the CNS conditions and SIJ pain were related to RM score. Only depression/anxiety and LLD were associated with gait speed. In this sample of older veterans, CLBP was a multifaceted condition. Both CNS and peripheral conditions were associated with self-reported and performance-based function. Additional investigation is required to determine the impact of treating these conditions on patient outcomes and health care utilization.

Sustained analgesic effect of clonidine co-polymer depot in a porcine incisional pain model.

BackgroundPrevious research suggests that the α2 adrenergic agonist clonidine, a centrally acting analgesic and antihypertensive, may also have direct effects on peripheral pain generators. However, aqueous injections are limited by rapid systemic absorption leading to off target effects and a brief analgesic duration of action.PurposeThe aim of this study was to examine the efficacy of a sustained-release clonidine depot, placed in the wound bed, in a pig incisional pain model.MethodsThe depot was a 15 mm ×5 mm ×0.3 mm poly(lactide-co-caprolactone) polymer film containing 3% (w/w) clonidine HCl (MDT3). Fifty-two young adult mix Landrace pigs (9–11 kg) were divided into seven groups. All subjects received a 6 cm, full-thickness, linear incision into the left lateral flank. Group 1 served as a Sham control group (Sham, n=8). Group 2 received three placebo strips (PBO, n=8), placed end-to-end in the subcutaneous wound bed before wound closure. Group 3 received one MDT3 and two PBO (n=8), Group 4 received two MDT3 and one PBO (n=8), and Group 5 received three MDT3 (n=8). Positive control groups received peri-incisional injections of bupivacaine solution (Group 6, 30 mg/day bupivacaine, n=8) or clonidine solution (Group 7, 225 µg/day, n=4).ResultsThe surgical procedure was associated with significant peri-incisional tactile allodynia. There was a dose-dependent effect of MDT3 in partially reversing the peri-incisional tactile allodynia, with maximum pain relief relative to Sham at 72 hours. Daily injections of bupivacaine (30 mg), but not clonidine (up to 225 µg), completely reversed allodynia within 48 hours. There was a statistically significant correlation between the dose of MDT3 and cumulative withdrawal threshold from 4 hours through the conclusion of the study on day 7.ConclusionThese data suggest that a sustained-release clonidine depot may be a viable nonopioid, nonamide anesthetic therapy for the treatment of acute postsurgical nociceptive sensitization.

The aetiologies of Failed Back Surgery Syndrome: A systematic review.

Four to fifty percent of patients will develop Failed Back Surgery Syndrome (FBSS) following lumbar spine surgery. Repeated surgeries lead to escalating costs and subsequent decreases in success rate. Much of the research to date has focused on the psychosocial factors associated with FBSS. All factors including physical and pathological aetiologies should be examined. These factors may be independent, co-exist with or predispose patients to the psychological factors associated with FBSS. Previous reviews on the topic have been limited by a lack of systematic overview. The aim of this review is to identify the physical, physiological and pathological aetiologies of FBSS. This review was done in accordance with the PRISMA guidelines. A computer-aided search of the electronic databases from inception to December 2014 was performed. Outcome measures of interest included pain, functional and radiological assessments. Two reviewers independently selected studies for inclusion. Methodological quality was assessed using the Newcastle Ottawa Scale. Six studies met the inclusion criteria and included a total of 663 patients. A total of twenty two aetiologies were identified. Only three studies reviewed non-surgical aetiologies. Many of the studies relied on medical imaging to identify the aetiologies. A meta-analysis was not undertaken due to the heterogeneity of studies. The causes of FBSS can be attributed to patho-anatomical, peripheral pain generators, physical/ mechanical, neurophysiological, surgical and `other' aetiologies. Three of the studies only examined surgical causes of FBSS. Further research, that examines surgical and non-surgical aetiologies, is required to draw firm conclusions. With nineteen aetiologies identified, FBSS remains an unclear diagnosis for a complex heterogeneous group of patients.

Central Sensitization Is Modulated Following Trigger Point Anesthetization in Patients with Chronic Pain from Whiplash Trauma. A Double-Blind, Placebo-Controlled, Crossover Study.

Central sensitization (CS) with low peripheral pain thresholds (PPTs) is a common finding among patients with chronic pain after whiplash (CPWI). While it has been proposed that myofascial myofascial trigger points (MTrPs) may act as modulators of central sensitization, previously reported findings are conflicting and inconclusive. The present study was designed to investigate immediate responsiveness of CS to alterations in nociceptive input. Controlled, double-blind, cross-over. Thirty-one patients with chronic pain (trapezius myalgia) and CS after whiplash. Participants were referred by randomization to group A for injection of a single peripheral pain generator (MTrP or other discrete tender point) with local anesthetic or to group B for sham injection and cross-over. Documentation of PPT (Algometer), maximum jaw opening (caliper), and grip strength (Vigorimeter), as well as subjective overall pain (visual analog scale [VAS]), was made before and after each intervention. Statistical analysis of data (Student's t test, analysis of variance) confirmed that peripheral pain thresholds were significantly higher and maximum jaw opening significantly greater after anesthetizing a focal pain generator in the trapezius, but not after a sham injection. In contrast with the objective variables, subjective generalized pain improved (VAS) after not only an injection of local anesthetic, but also, and to a similar extent, after a sham injection. CS, as expressed by lowered PPT, is a rapidly adjusting physiological response to nociceptive stimuli in some patients with chronic pain after whiplash. PPT are likely modulated by myofascial tender points in selected patients with CS. With reference to the present findings, surgical ablation of MTrPs is discussed as a potential treatment modality for CS.

First European Congress on Hereditary ATTR amyloidosis.

Familial amyloidosis typically causes a nerve length-dependent small fiber polyneuropathy that starts in the feet with loss of temperature and pain sensations, associated with autonomic dysfunction, which can be extremely severe and life threatening. Neuropathic pain is commonly associated with amyloid neuropathy. There are no randomized controlled trials in peripheral neuropathies specifically related to familial amyloidosis. However meta-analyses have confirmed that the efficacy of drugs against neuropathic pain generally is not linked to the aetiology of pain and therefore the drugs found effective in other painful polyneuropathies may benefit to patients with amyloid neuropathies [1]. Recently the Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain has updated evidence-based recommendations for pharmacotherapy of neuropathic pain [1] using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Pregabalin, gabapentin, serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressants particularly duloxetine, and tricyclic antidepressants (TCAs) received strong GRADE recommendations for use and are recommended as first-line for peripheral neuropathic pain, although with caution as regards TCAs. Capsaicin high concentration patches, lidocaine patches and tramadol received weak GRADE recommendation for use and are recommended as generally second line for peripheral neuropathic pain and local pain generator. Strong opioids and botulinum toxin type A (BTX-A received weak GRADE recommendations for use mainly because of efficacy in most trials but safety concerns (opioids) or lower quality of evidence (BTX-A). These drugs are recommended as third line by specialist use as regards BTX-A. There was a weak GRADE recommendation against the use of oromucosal cannabinoids (Sativex) and valproate and strong GRADE recommendations against the use of levetiracetam and mexiletine because of generally negative results and safety concerns (mexiletine). Other drug treatments (e.g. other antiepileptics, antidepressants and topical treatments, tapentadol and NMDA antagonists) or combination therapy received inconclusive GRADE recommendations because of generally discrepant findings, although some of these drugs might be effective in subgroups of patients. These drugs can be recommended in familial amyloid neuropathy, but topical agents have a major advantage in this context because of their low risk of systemic side effects.

Central and peripheral pain generators in women with chronic pelvic pain: patient centered assessment and treatment.

Women with chronic pelvic pain (CPP) often present without obvious cause on imaging studies, laboratory values or physical exam. Dysfunctional sensory processing in the central nervous system (CNS) may explain pain of unclear origin. Central sensitization (CS), a mechanism of centrally mediated pain, describes this abnormal processing of sensory information. Women with CPP often present with several seemingly unrelated symptoms. This can be explained by co-existing chronic pain syndromes occurring in the same patient. Central sensitization occurs in all of these pain syndromes, also described as dysfunctional pain syndromes, and thus may explain why several often occur in the same patient. Six of the most common pain disorders that co-exist in CPP include endometriosis, painful bladder syndrome/interstitial cysitis, vulvodynia, myofascial pain/ pelvic floor hypertonus, irritable bowel syndrome, and primary dysmenorrhea. Central pain generators, (pain originating from CS) and peripheral pain generators, (pain from local tissue damage), can both occur in each of these six conditions. These pain generators will be described. Chronic pain, specifically dysfunctional sensory processing, is recognized as a systemic disease process like diabetes to be managed as opposed to a local problem to be "fixed" or cured. A multi-disciplinary approach to assessment and treatment with a focus on improving emotional, physical and social functioning instead of focusing strictly on pain reduction is more effective in decreasing disability. This is best achieved by determining the patient's needs and perspective through a patient-centered approach. Algorithms for such an approach to assessment and treatment are outlined.

Neuropathic pain mechanisms and imaging.

Molecular and cellular imaging of neuropathic pain, utilizing the myriad of receptors and inflammatory mediators involved in nociceptive activity, is a promising approach toward objectively identifying peripheral pain generators. Neuropathic conditions arise from injured and inflamed nerves, which have been shown to elaborate several molecular and cellular elements that give rise to the neuropathic phenotype and can be exploited for imaging purposes. As such, in vivo approaches to image neuropathic pain mechanisms include imaging voltage-gated sodium channels with radiolabeled saxitoxin, calcium signaling with manganese-enhanced magnetic resonance imaging, and inflammatory changes and nerve metabolism with (18)F-fluorodeoxyglucose. Imaging approaches exploiting other mediators of nociceptive activity, such as substance P (neurokinin-1) receptor, sigma-1 receptor, and macrophages, have shown promising early advances in animal models. By combining the sensitivity and specificity of molecular imaging with the high anatomical, spatial and contrast resolution afforded by computed tomography and MRI, radiologists can potentially identify sites of nerve injury or neuroinflammation that are implicated as peripheral pain drivers with greater accuracy and confidence. In addition to guiding therapy, these approaches will aid in new drug designs for analgesia and more individualized treatment options.

Muscle pain syndrome: Evaluation and treatment

Muscle pain syndrome: Evaluation and treatment

Management of fibromyalgia in older adults.

Fibromyalgia (FM) is a pain syndrome characterized by dysregulation of pain-processing mechanisms. FM may arise de novo or evolve following nervous system sensitization after an identifiable triggering event or related to a peripheral pain generator such as osteoarthritis. Although the focus symptom of FM is generalized body pain, patients may also experience sleep and mood disturbance, fatigue, and other somatic symptoms leading to the concept of a polysymptomatic condition. In view of prevalent other comorbidities in older patients, FM may be overlooked and management may be neglected, thereby contributing to poor well-being. Pertinent to the older patient is to ensure that the diagnosis of FM is correct and that other conditions are not misdiagnosed as FM. Whereever possible, treatment strategies should emphasize non-pharmacologic interventions that encompass healthy lifestyle habits, with attention to adequate physical activity in particular. Drug treatments should be tailored to the individual needs of the patient, with knowledge that they may offer only a modest effect, but with caution to ensure that adverse effects do not overshadow therapeutic effects.

Re: Are Peripheral Pain Generators Important in Fibromyalgia and Chronic Widespread Pain?

Dear Dr. Gallagher, We appreciated Dr Gerwin's editorial [1] reflecting on the interesting Albrecht et al. study “Excessive peptidergic sensory innervation of cutaneous arteriole–venule shunts (AVS) in the palmar glabrous skin of fibromyalgia patients: Implications of wide-spread deep tissue pain and fatigue” [2]. Dr. Gerwin summarizes the findings by Albrecht et al. [2]—“that changes in blood flow and increased thermal sensitivity may each contribute to local palmar pain”—and asserts that thereby “they contribute to peripheral nerve sensitization which gives rise to local pain as well as contributing to central sensitization and central pain.” In the article we could not find the evidence for this assertion, which is notable for proclaiming that peripheral nerve sensitization is the fundamental “driver” of all possible somatic mechanisms of pain in this syndrome. Dr. Gerwin states, “It is the reduction …

Intense focused ultrasound stimulation can safely stimulate inflamed subcutaneous tissue and assess allodynia.

BackgroundPotential peripheral sources of deep pain can require invasive evocative tests for their assessment. Here we perform research whose ultimate goal is development of a non-invasive evocative test for deep painful tissue.MethodsWe used a rat model of inflammation to show that intense focused ultrasound (iFU) differentially stimulates inflamed versus control tissue and can identify allodynia. To do so we applied iFU to inflamed and normal tissue below the skin of rats’ hind paws and measured the amount of ultrasound necessary to induce paw withdrawal.ResultsiFU of sufficient strength (spatial and temporal average intensities ranged from 100–350 W/cm2) caused the rat to withdraw its inflamed paw, while the same iFU applied to the contralateral paw failed to induce withdrawal, with sensitivity and specificity generally greater than 90%. iFU stimulation of normal tissue required twice the amount of ultrasound to generate a withdrawal than did inflamed tissue, thereby assessing allodynia. Finally, we verified in a preliminary way the safety of iFU stimulation with acute histological studies coupled with mathematical simulations.ConclusionsGiven that there exist systems to guide iFU deep to the skin, image-guided iFU may one day allow assessment of patient’s deep, peripheral pain generators.

Are Peripheral Pain Generators Important in Fibromyalgia and Chronic Widespread Pain?

Fibromyalgia (FM) is a chronic widespread pain syndrome (CWPS) that is generally considered to be the result of a dysfunctional central pain modulating system. It is thought to importantly involve the descending pain inhibitory system. FM is known to be associated with multimodal hypersensitivity: mechanical, thermal, visual, and auditory. It is associated with a variety of comorbid conditions including irritable bowel syndrome, painful bladder, migraine headache, and temporo-mandibular joint syndrome. The relationship of the comorbid conditions to FM has not been clear. They can be considered to be the result of hyper-effective ascending central pain transmission resulting from deficient descending pain inhibition, or they can be considered as clinical entities in themselves, whose importance in FM lies in their acting as peripheral pain generators that enhance or initiate central sensitization, thereby contributing to chronic widespread pain. There may, of course, be some truth in both of these concepts. The presence of peripheral pain generators that lead to central sensitization initiating or maintaining CWPS or FM remains controversial, however. This question is addressed in a masterful study by Albrecht et al. ⇓ …

Myofascial trigger points: spontaneous electrical activity and its consequences for pain induction and propagation

Active myofascial trigger points are one of the major peripheral pain generators for regional and generalized musculoskeletal pain conditions. Myofascial trigger points are also the targets for acupuncture and/or dry needling therapies. Recent evidence in the understanding of the pathophysiology of myofascial trigger points supports The Integrated Hypothesis for the trigger point formation; however unanswered questions remain. Current evidence shows that spontaneous electrical activity at myofascial trigger point originates from the extrafusal motor endplate. The spontaneous electrical activity represents focal muscle fiber contraction and/or muscle cramp potentials depending on trigger point sensitivity. Local pain and tenderness at myofascial trigger points are largely due to nociceptor sensitization with a lesser contribution from non-nociceptor sensitization. Nociceptor and non-nociceptor sensitization at myofascial trigger points may be part of the process of muscle ischemia associated with sustained focal muscle contraction and/or muscle cramps. Referred pain is dependent on the sensitivity of myofascial trigger points. Active myofascial trigger points may play an important role in the transition from localized pain to generalized pain conditions via the enhanced central sensitization, decreased descending inhibition and dysfunctional motor control strategy.