New updates on transcranial magnetic stimulation in chronic pain.

PURPOSE OF REVIEW: Chronic pain is the most prevalent symptomatic disease worldwide. Nonpharmacological interventions, such as noninvasive neuromodulation (NIN), have gained scientific evidence to support their use as an add-on strategy to pharmacological pain management. The most studied NIN technique is repetitive transcranial magnetic stimulation (rTMS). This review aims to identify the current indications for rTMS in the treatment of chronic pain and its new perspectives. RECENT FINDINGS: High-frequency rTMS delivered to the primary motor cortex (M1) is currently a treatment strategy with the most literature support for decreased pain intensity and alleviation of associated symptoms in peripheral neuropathic pain, fibromyalgia and migraine. It has been shown that stimulation sessions are well tolerated and tolerable, and the effects of daily stimulation sessions can be prolonged by spaced maintenance stimulation sessions. Despite its efficacy, some individuals will not respond to rTMS targeted to M1. Lines of research are currently being developed to improve rTMS efficacy either by exploring new therapeutic targets, using novel stimulation parameters or more comprehensively profiling patients who are likely to respond to this treatment modality. SUMMARY: Noninvasive brain stimulation for chronic TMS pain is a well tolerated and reasonable add-on treatment approach for pain syndromes such as neuropathic pain, migraine and fibromyalgia. Strategies to improve its efficacy are an active field of research.

Multisensory Sensitivity is Related to Deep-Tissue but Not Cutaneous Pain Sensitivity in Healthy Individuals.

PURPOSE: Some individuals with chronic pain find daily life sensations (eg, noise, light, or touch) aversive. This amplification of multisensory sensations has been associated with centrally mediated plasticity; for example, greater multisensory sensitivity (MSS) occurs in patients with fibromyalgia than rheumatoid arthritis. However, whether MSS preferentially relates to pain measures which reflect central influences (eg, dynamic quantitative sensory testing (QST) or referred pain), or whether the MSS-pain relationship requires priming from chronic pain, is unknown. Thus, this cross-sectional study investigated the relationships between MSS assessed in a pain-free state and evoked pain sensitivity. METHODS: Experimental intramuscular infusion pain and multiple static and dynamic QST were assessed in 465 healthy, pain-free adults: pain thresholds using pressure (PPTs) and heat (HPTs), temporal summation of pain (TSP) using pressure, heat or punctate stimuli, and conditioned pain modulation (CPM) using pressure or heat test stimuli. MSS was assessed using 7 items from Barsky's Somatosensory Amplification Scale. Differences in pain and QST between sex-specific MSS quartiles were assessed, adjusting for multiple comparisons. All participants completed at least one intramuscular infusion condition, but not all were asked to complete each QST (n=166-465). RESULTS: Both static and dynamic QST differed between highest and lowest MSS quartiles using pressure stimuli: lower PPTs (adjusted-p<0.01); increased pressure TSP (adjusted-p=0.02); lower pressure CPM (adjusted-p=0.01). However, none of the heat or punctate QST measures (HPTs, TSP, or CPM) differed between MSS quartiles (adjusted-p>0.05). Odds of experiencing TSP or referred pain was not greater, whereas CPM was 8-fold less likely, in those with highest MSS. CONCLUSION: Normal variation in non-noxious MSS is related to both static and dynamic pain sensitivity, without sensitization associated with chronic pain, but is dependent on the QST stimulus. Thus, common influences on MSS and pain sensitivity may involve central mechanisms but are likely more complex than previously recognized.

Testosterone replacement therapy of opioid-induced male hypogonadism improved body composition but not pain perception: a double-blind, randomized, and placebo-controlled trial.

BACKGROUND: Hypogonadism is prevalent during opioid treatment, but the effect of testosterone replacement treatment (TRT) on body composition, pain perception, and adrenal function is unclear. PURPOSE: To measure changes in body composition, pain perception, quality of life, and adrenal function after TRT or placebo in opioid-treated men with chronic non-malignant pain. METHODS: Double-blind, placebo-controlled study in 41 men (>18 years) with total testosterone <12 nmol/L were randomized to 24 weeks TRT (Testosterone undecanoate injection three times/6 months, n = 20) or placebo (placebo-injections, n = 21). OUTCOMES: Body composition (lean body mass and fat mass assessed by DXA), clinical pain intensity (numerical rating scale), and experimental pain perception (quantitative sensory assessment), quality of life (SF36), and adrenocorticotrophic hormone (ACTH) test. Data were presented as median (quartiles). Mann-Whitney tests were performed on delta values (24-0 weeks) between TRT and placebo. RESULTS: The median age was 55 years (46; 59) and total testosterone before intervention was 6.8 (5.0; 9.3) nmol/L. TRT was associated with change of testosterone levels: 12.3 (7.0; 19.9) nmol/L (P < 0.001 vs placebo), increased lean body mass: 3.6 (2.3; 5.0) kg vs 0.1 kg (-2.1; 1.5) during TRT vs placebo and decreased total fat mass: -1.2 (-3.1; 0.7) kg vs 1.2 kg (-0.9; 2.5) kg, both P < 0.003. Changed pain perception, SF36, and ACTH-stimulated cortisol levels were non-significantly changed during TRT compared with placebo. CONCLUSIONS: Six months of TRT improved body composition in men with opioid-induced hypogonadism without significant changes in outcomes of pain perception, quality of life, or adrenal function.

Experimental knee-related pain enhances attentional interference on postural control.

PURPOSE: To quantify how postural stability is modified during experimental pain while performing different cognitively demanding tasks. METHODS: Sixteen healthy young adults participated in the experiment. Pain was induced by intramuscular injection of hypertonic saline solution (1 mL, 6%) in both vastus medialis and vastus lateralis muscles (0.9% isotonic saline was used as control). The participants stood barefoot in tandem position for 1 min on a force plate. Center of pressure (CoP) was recorded before and immediately after injections, while performing two cognitive tasks: (i) counting forwards by adding one; (ii) counting backwards by subtracting three. CoP variables-total area of displacement, velocity in anterior-posterior (AP-velocity) and medial-lateral (ML-velocity) directions, and CoP sample entropy in anterior-posterior and medial-lateral directions were displayed as the difference between the values obtained after and before each injection and compared between tasks and injections. RESULTS: CoP total area ( - 84.5 ± 145.5 vs. 28.9 ± 78.5 cm2) and ML-velocity ( - 1.71 ± 2.61 vs. 0.98 ± 1.93 cm/s) decreased after the painful injection vs. Control injection while counting forward (P < 0.05). CoP total area (12.8 ± 53.9 vs. - 84.5 ± 145.5 cm2), ML-velocity ( - 0.34 ± 1.92 vs. - 1.71 ± 2.61 cm/s) and AP-velocity (1.07 ± 2.35 vs. - 0.39 ± 1.82 cm/s) increased while counting backwards vs. forwards after the painful injection (P < 0.05). CONCLUSION: Pain interfered with postural stability according to the type of cognitive task performed, suggesting that pain may occupy cognitive resources, potentially resulting in poorer balance performance.

Preoperative Neuropathic Pain-like Symptoms and Central Pain Mechanisms in Knee Osteoarthritis Predicts Poor Outcome 6 Months After Total Knee Replacement Surgery.

Preoperative pain characteristics in patients with osteoarthritis may explain persistent pain after total knee replacement. Fifty patients awaiting total knee replacement and 22 asymptomatic controls were recruited to evaluate the degree of neuropathic pain symptoms and pain sensitization. Patients with OA were pain phenotyped into 2 groups based on the PainDETECT questionnaire: high PainDETECT group (scores ≥19) indicating neuropathic pain-like symptoms and low PainDETECT group (scores <19) indicating nociceptive or mixed pain. Cuff algometry assessing pain detection thresholds and pain tolerance thresholds was conducted on the lower legs. Temporal summation of pain was assessed using 10 sequential cuff stimulations and a von Frey stimulator. Conditioning pain modulation was assessed by cuff pain conditioning on 1 leg and parallel assessment of pain detection thresholds on the contralateral leg. Pressure pain thresholds were recorded by pressure handheld algometry local and distant to the knee. Knee pain intensity (visual analogue scale) and pain assessments were collected before and 6 months after total knee replacement. Thirty percent of patients demonstrated neuropathic pain-like symptoms (high PainDETECT group). Facilitated temporal summation of pain and reduced pressure pain thresholds distant to the knee were found in the high PainDETECT group compared with the low PainDETECT group and healthy controls (P < .001). Patients with OA with high PainDETECT scores had higher postoperative visual analogue scale pain scores than the low PainDETECT patients (P < .0001) and facilitated temporal summation of pain (P = .022) compared with healthy control subjects. Perspective: This study has found that preoperative PainDETECT scores independently predict postoperative pain. Patients with knee OA with neuropathic pain-like symptoms identified using the PainDETECT questionnaire are most at risk of developing chronic postoperative pain after TKR surgery.

Differences in Pain Processing Between Patients with Chronic Low Back Pain, Recurrent Low Back Pain, and Fibromyalgia.

BACKGROUND: The impairment in musculoskeletal structures in patients with low back pain (LBP) is often disproportionate to their complaint. Therefore, the need arises for exploration of alternative mechanisms contributing to the origin and maintenance of non-specific LBP. The recent focus has been on central nervous system phenomena in LBP and the pathophysiological mechanisms underlying the various symptoms and characteristics of chronic pain. Knowledge concerning changes in pain processing in LBP remains ambiguous, partly due to the diversity in the LBP population. OBJECTIVE: The purpose of this study is to compare quantitative sensory assessment in different groups of LBP patients with regard to chronicity. Recurrent low back pain (RLBP), mild chronic low back pain (CLBP), and severe CLBP are compared on the one hand with healthy controls (HC), and on the other hand with fibromyalgia (FM) patients, in which abnormal pain processing has previously been reported. STUDY DESIGN: Cross-sectional study. SETTING: Department of Rehabilitation Sciences, Ghent University, Belgium. METHODS: Twenty-three RLBP, 15 mild CLBP, 16 severe CLBP, 26 FM, and 21 HC participated in this study. Quantitative sensory testing was conducted by manual pressure algometry and computer-controlled cuff algometry. A manual algometer was used to evaluate hyperalgesia as well as temporal summation of pain and a cuff algometer was used to evaluate deep tissue hyperalgesia, the efficacy of the conditioned pain modulation and spatial summation of pain. RESULTS: Pressure pain thresholds by manual algometry were significantly lower in FM compared to HC, RLBP, and severe CLBP. Temporal summation of pain was significantly higher in FM compared to HC and RLBP. Pain tolerance thresholds assessed by cuff algometry were significantly lower in FM compared to HC and RLBP and also in severe CLBP compared to RLBP. No significant differences between groups were found for spatial summation or conditioned pain modulation. LIMITATIONS: No psychosocial issues were taken into account for this study. CONCLUSION: The present results suggest normal pain sensitivity in RLBP, but future research is needed. In mild and severe CLBP some findings of altered pain processing are evident, although to a lesser extent compared to FM patients. In conclusion, mild and severe CLBP presents within a spectrum, somewhere between completely healthy persons and FM patients, characterized by pain augmentation.

Decreased QOL and muscle strength are persistent 1 year after intramedullary nailing of a tibial shaft fracture: a prospective 1-year follow-up cohort study.

INTRODUCTION: To evaluate the development in patient-reported quality of life (QOL) and muscle strength in the period from surgery to 12 months postoperatively after intramedullary nailing of a tibial shaft fracture. MATERIALS AND METHODS: The design was a prospective, follow-up cohort study. QOL was measured with the questionnaire Eq5D-5L and compared to norm data from a reference population. Recordings of pain and contralateral muscle strength (isometric maximal voluntary contraction (MVC) for knee flexion and extension were collected at 6 weeks, 3, 6, and 12 months postoperatively. Ipsilateral MVCs were recorded at 6 and 12 months. RESULTS: Forty-nine patients were included. The mean age at the time of fracture was 43.1 years (18-79 years). Twelve months postoperatively, the mean Eq5D-5L index was 0.792 (95 % CI 0.747-0.837). Throughout the 12 months postoperatively, patients reported worse QOL compared to the reference population. Six and 12 months after surgery patients demonstrated decreased muscle strength in the injured leg compared to the non-injured leg for knee extension and flexion (P < 0.001). Twelve months postoperatively, increasing relative difference in muscle strength during knee extension show a fair correlation to worse QOL (R = 0.541, P < 0.001). CONCLUSIONS: Throughout the 12 months postoperatively, patients reported worse QOL compared to the reference population. Muscle strength in the non-injured leg improved over time and was higher after 6 and 12 months compared with the injured leg.

Preoperative pain mechanisms assessed by cuff algometry are associated with chronic postoperative pain relief after total knee replacement.

Chronic postoperative pain after total knee replacement (TKR) in knee osteoarthritis (KOA) implies clinical challenges. Widespread hyperalgesia, facilitated temporal summation of pain (TSP), and impaired conditioned pain modulation (CPM) have been found in painful KOA. This exploratory study investigated postoperative pain relief 12 months after TKR in 4 subgroups of patients preoperatively profiled by mechanistic quantitative sensory testing. In 103 patients with KOA, pressure pain detection threshold (PDT) and tolerance thresholds (PTT) were assessed at the lower leg using cuff algometry. Temporal summation of pain was measured as an increase in pain intensity scores during 10 repeated (2 seconds intervals) painful cuff stimuli. Conditioned pain modulation was calculated as the relative increase in PDT during painful conditioning stimulation. The grand averages of TSP and CPM were calculated and values below or above were used for subgrouping: facilitated TSP/impaired CPM (group A, N = 16), facilitated TSP/normal CPM (group B, N = 15), normal TSP/impaired CPM (group C, N = 44), and normal TSP/normal CPM (group D, N = 28). Clinical VAS pain intensity scores were collected before and 12 months after TKR surgery and the pain relief calculated. Less pain relief was found in group A (52.0% ± 14.0% pain relief) than in group B (81.1% ± 3.5%, P = 0.023) and group C (79.6% ± 4.4%, P = 0.007), but not group D (69.4% ± 7.9%, P = 0.087). Low preoperative PDT was associated with a less postoperative pain relief (R = -0.222, P = 0.034), whereas TSP or CPM alone showed no associations with postoperative pain relief. This explorative study indicated that patients with osteoarthritis with facilitated TSP together with impaired CPM are more vulnerable to experience less pain relief after TKR.

Local and Widespread Hyperalgesia After Isolated Tibial Shaft Fractures Treated with Intramedullary Nailing.

OBJECTIVES: Knee pain is accepted as a common complication to intramedullary nailing of tibial fractures. However, no studies have systematically studied the pain sequel following tibial fractures. The objective of this study was to assess pain and hyperalgesia from 6 weeks to 12 months postoperatively after intramedullary nailing of tibial shaft fracture. METHODS: A total of 39 patients were included in this 12-month follow-up study. After 6 weeks, 3, 6, and 12 months postoperatively the pain intensity was measured on a visual analog scale (VAS) and the pressure pain sensitivity was assessed bilaterally by pain pressure thresholds (PPTs). RESULTS: The mean age at the time of fracture was 42.9 years. Twelve months after surgery, the pain intensity for worst pain during the last 24 hours was 1.8 ± 2.7 cm. The PPTs progressively increased from 6 weeks after surgery to 12 months postoperatively for all PPT sites except for the forearm (P < 0.012). Moreover, the PPTs on the leg were generally reduced on the injured side compared with the non-injured side (P < 0.04). CONCLUSIONS: This study suggests that localized, distal, and bilateral hyperalgesia are common following an isolated tibial shaft fracture treated with intramedullary nailing, although no widespread (extrasegmental) hyperalgesia was detected. Such observations may be important for developing the most adequate rehabilitation procedure following a tibial fracture.

The effects of experimental knee pain on lower limb corticospinal and motor cortex excitability.

INTRODUCTION: Notable weakness of the quadriceps muscles is typically observed as a consequence of knee joint arthritis, knee surgery and knee injury. This is partly due to ongoing neural inhibition that prevents the central nervous system from fully activating the quadriceps, a process known as arthrogenic muscle inhibition (AMI). To investigate the mechanisms underlying AMI, this study explored the effects of experimental knee pain on lower limb corticospinal and motor cortex excitability. METHODS: Twenty-four healthy volunteers participated in this study. In experiment 1, experimental knee pain was induced by the injection of hypertonic saline into the infrapatellar fat pad (n = 18). In experiment 2, isotonic saline was injected into the fat pad as a non-painful control (n = 8). Pain intensity was measured on a 10-cm electronic visual analogue scale. Transcranial magnetic stimulation and electromyography were used to measure lower limb motor-evoked potential amplitude and short-interval intracortical inhibition before and after the injection. RESULTS: The peak VAS score following hypertonic saline (5.0 ± 0.5 cm) was higher than after isotonic saline (p <0.001). Compared with baseline, there was a significant increase in vastus lateralis (p = 0.02) and vastus medialis motor-evoked potential amplitude (p = 0.02) during experimental knee pain that was not apparent during the control condition. Biceps femoris and tibialis anterior motor-evoked potential amplitude did not change following injection (all p >0.05). There was no change in short-interval intracortical inhibition measured from vastus lateralis following injection (both p >0.05). CONCLUSIONS: Quadriceps corticospinal excitability increases during experimental knee pain, providing no evidence for a supraspinal contribution to quadriceps AMI.

MR-guided focused ultrasound for the novel and innovative management of osteoarthritic knee pain.

BACKGROUND: Severe knee pain associated with osteoarthritis (OA) is one of the most common and troublesome symptoms in the elderly. Recently, local bone denervation by MR-guided focused ultrasound (MRgFUS) has been demonstrated as a promising tool for pain palliation of bone metastases. The purpose of this study was to develop a novel treatment for knee OA using MRgFUS, and to validate its safety and efficacy. METHODS: Eight patients with medial knee pain and eligible for total knee arthroplasty were included. MR-guided focused sonication treatments were applied to bone surface just below the rim osteophyte of medial tibia plateau with real-time monitoring of the temperature in the target sites. The pain intensity during walking was assessed on a 100 mm visual analog scale (VAS) before and after treatment. Pressure pain thresholds (PPTs) were also evaluated over several test sites adjacent to the sonication area and control sites one month after treatment. RESULTS: Six patients (75%) showed immediate pain alleviation after treatment, and four of them demonstrated long-lasting effect at 6-month follow up (mean VAS reduction; 72.6%). In responders, PPTs in medial knee were significantly increased after treatment (Median; pre- 358 kpa vs post- 534 kpa, p < 0.0001). There were no adverse side effects or complications during and after treatment. CONCLUSIONS: These initial results illustrate the safety and efficacy of the newly developing MRgFUS treatment. Significant increase of PPTs on treated area showed successful denervation effect on the nociceptive nerve terminals. MRgFUS is a promising and innovative procedure for noninvasive pain management of knee OA. TRIAL REGISTRATION: Trial Registration: UMIN000010193.

Relating clinical measures of pain with experimentally assessed pain mechanisms in patients with knee osteoarthritis.

Background Peripheral and central sensitisation is prominent in knee osteoarthritis (KOA) and could be important for the reduced efficacy in some cases after as well surgery as pharmacological interventions. Although sensitisation is important in KOA it is not known to what degree it contributes to the overall clinical pain problem. The aim was therefore to investigate how much a combination of quantitative pain measures assessing various pain mechanisms (local and spreading hyperalgesia, temporal and spatial summation, descending inhibition) could predict peak pain intensity in patients with KOA. Methods While resting in a comfortable recumbent position the pressure pain thresholds (PPT) in the peripatellar region (eight locations) and at the tibialis anterior muscle (TA) were assessed by handheld pressure algometry, computer-controlled pressure algometry and cuff-algometry in the affected leg of 17 KOA patients without pain or sensory dysfunctions in other regions than the knee. Cuff-algometry was used to detect spatial pain summation of the lower leg. Temporal pain summation was assessed by repeated pressure stimulation on the TA muscle. The conditioning pain modulation (CPM) was evaluated by conditioning tonic arm pain and by PPT from the peripatellar region. The participants rated their peak pain intensity in the previous 24 h using on a 10 cm visual analogue scale. Results A multiple-regression model based on TA pressure pain sensitivity (spreading sensitisation) and temporal pain summation on the lower leg accounted for 55% of the variance in peak pain intensity experienced by the patients (P=0.001). Significant correlations (P< 0.05) were found between PPTs assessed by handheld pressure algometry in the peripatellar region and at TA (R = 0.94), PPTs assessed by computer-controlled pressure algometry and handheld pressure algometry in the peripatellar region (R = 0.71), PPTs assessed by computer-controlled pressure algometry in the peripatellar region and handheld pressure algometry at TA (R = 0.71) and temporal summation at the knee and at TA (R = 0.73). Conclusion Based on the multiple regression model 55% variance of the perceived maximal pain intensity in painful KOA could be explained by the quantitative experimental pain measures reflecting central pain mechanisms (spreading sensitisation, temporal summation). The lack of other correlations between the methods used in assessing pain mechanisms in this study highlights the importance of applying different tests and different pain modalities when assessing the sensitised pain system as different methods add complementary information. Implications Clinical pain intensity can be explained by influences of different central pain mechanisms in KOA. This has implications for pain management in KOA where treatment addressing central pain components may be more important than previously acknowledged.

Translational musculoskeletal pain research.

Diagnosis and management of musculoskeletal pain is a major clinical challenge. Fundamental knowledge of nociception from deep somatic structures and related mechanisms of sensitisation have been characterised in animals but the translation into clinical sciences is still lacking. Development and refinement of mechanism-based quantitative sensory testing in healthy volunteers and pain patients have provided new opportunities to assess pain and hyperalgesic reactions. The current technologies can provide information about, for example, peripheral and central sensitisation, descending pain control, central integration and structure specific sensitisation. Such a mechanistic approach can be used for differentiated diagnosis and for target validating new and existing analgesics. Mechanistic pain assessment of new compounds under development provides opportunities for target validation in proof-of-concept studies, which generate information to be used for selecting the most optimal patients for later clinical trials. New safe and efficient compounds are highly needed in the area of musculoskeletal pain management.

Reproduction of overall spontaneous pain pattern by manual stimulation of active myofascial trigger points in fibromyalgia patients.

INTRODUCTION: It has previously been reported that local and referred pain from active myofascial trigger points (MTPs) in the neck and shoulder region contribute to fibromyalgia (FM) pain and that the pain pattern induced from active MTPs can reproduce parts of the spontaneous clinical FM pain pattern. The current study investigated whether the overall spontaneous FM pain pattern can be reproduced by local and referred pain from active MTPs located in different muscles. METHODS: A spontaneous pain pattern in FM was recorded in 30 FM patients and 30 healthy subjects served as controls. Local and referred pain patterns induced from active (patients) and latent (controls) MTPs were recorded following manual stimulation. The existence of MTPs was confirmed by intramuscular electromyographical registration of spontaneous electrical activity. RESULTS: Local and referred pain areas induced from key active MTPs in FM were larger than pain areas from latent MTPs in healthy controls (P < 0.001), but were similar to the overall spontaneous FM pain area in FM (P > 0.05). The induced pain area was positively associated with current spontaneous pain intensity in FM (P < 0.01). The locations of key active MTPs in FM patients were found to have latent MTPs in healthy subjects. The muscles containing key active MTPs in FM are often observed in the muscles of extensor digitorum, trapezius, infraspinatus in the upper part of the body and of quadratus lumborum, gluteus medius in the lower part of the body. CONCLUSIONS: The overall spontaneous FM pain pattern can be reproduced by mechanical stimulation of active MTPs located in different muscles, suggesting that fibromyalgia pain is largely composed of pain arising from muscle pain and spasm. Targeting active MTPs and related perpetuating factors may be an important strategy in FM pain control. TRIAL REGISTRATION: ISRCTN ISRCTN43167547.

Assessment of mechanisms in localized and widespread musculoskeletal pain.

The aim of this Review is to give a short presentation of the manifestations, assessment methods, and mechanisms underlying localized and widespread musculoskeletal pain, deep somatic tissue hyperalgesia and chronification. Hyperalgesia can be explained by increased pain sensitivity of nociceptors located in deep tissue (peripheral sensitization) or by increased responses from dorsal horn neurons (central sensitization). The spreading of pain and sensitization is related to increased synaptic activity in central neurons and to changes in descending control from supraspinal centers. Manifestations related to the different aspects of sensitization can be assessed quantitatively using sensory tests, such as pressure algometry (quantitative palpation) and cuff-algometry. Repeated pressure stimulation can evaluate the degree of temporal summation, which is a proxy for the level of central sensitization, as is expanded referred muscle pain area. The transition of acute localized musculoskeletal pain into chronic widespread pain is related to the progression of peripheral and central sensitization. This sensitization for the chronification of pain should be assessed by adequate pain biomarkers. Furthermore, pain prevention should target early intervention strategies and new anti-hyperalgesic compounds should be developed.

The predetermined sites of examination for tender points in fibromyalgia syndrome are frequently associated with myofascial trigger points.

UNLABELLED: The aim of this present study is to test the hypotheses that the 18 predetermined sites of examination for tender points (TP sites) in fibromyalgia syndrome (FMS) are myofascial trigger points (MTrPs), and that the induced pain from active MTrPs at TP sites may mimic fibromyalgia pain. Each TP site was evaluated with manual palpation followed by intramuscular electromyographic (EMG) registration of spontaneous electrical activity to confirm or refute the existence of an MTrP in 30 FMS patients. Overall spontaneous pain intensity and pain pattern were recorded before manual identification of MTrPs. Local and referred pain pattern from active MTrPs were drawn following manual palpation at TP sites. RESULTS: Showed that most of the TP sites are MTrPs. Local and referred pain from active MTrPs reproduced partly the overall spontaneous pain pattern. The total number of active MTrPs (r = .78, P < .0001), but not latent MTrPs (r = -.001, P = .99), was positively correlated with spontaneous pain intensity in FMS. The current study provides first evidence that pain from active MTrPs at TP sites mimics fibromyalgia pain. MTrPs may relate to generalized increased sensitivity in FMS due to central sensitization. PERSPECTIVE: This article underlies the importance of active MTrPs in FMS patients. Most of the TP sites in FMS are MTrPs. Active MTrPs may serve as a peripheral generator of fibromyalgia pain and inactivation of active MTrPs may thus be an alternative for the treatment of FMS.

Contribution of the local and referred pain from active myofascial trigger points in fibromyalgia syndrome.

The generalized hypersensitivity associated with fibromyalgia syndrome (FMS) may in part be driven by peripheral nociceptive sources. The aim of the study was to investigate whether local and referred pain from active myofascial trigger points (MTrPs) contributes to fibromyalgia pain. FMS patients and healthy controls (n=22 each, age- and gender-matched) were recruited. The surface area over the upper trapezius muscle on each side was divided into 13 sub-areas (points) of 1cm in diameter for each point. Pressure pain threshold (PPT) and the local and referred pain pattern induced by manual palpation at 13 points bilaterally in the upper trapezius were recorded. Results showed that PPT levels at all measured points were significantly lower in FMS than controls. Multiple active MTrPs (7.4+/-2.2) were identified bilaterally in the muscle in FMS patients, but no active MTrPs were found in controls. The mid-fiber region of the muscle had the lowest PPT level with the largest number of active MTrPs in FMS and with the largest number of latent MTrPs in controls. The local and referred pain pattern induced from active MTrPs bilaterally in the upper trapezius muscle were similar to the ongoing pain pattern in the neck and shoulder region in FMS. In conclusion, active MTrPs bilaterally in the upper trapezius muscle contribute to the neck and shoulder pain in FMS. Active MTrPs may serve as one of the sources of noxious input leading to the sensitization of spinal and supraspinal pain pathways in FMS.

Computerized cuff pressure algometry: A new method to assess deep-tissue hypersensitivity in fibromyalgia.

The aim of this study was to evaluate the use of computerized cuff pressure algometry (CPA) in fibromyalgia (FM) and to correlate deep-tissue sensitivity assessed by CPA with other disease markers of FM. Forty-eight women with FM and 16 healthy age-matched women were included. A computer-controlled, pneumatic tourniquet cuff was placed over the gastrocnemius muscle. The cuff was inflated, and the subject rated the pain intensity continuously on an electronic Visual Analogue Scale (VAS). The subject stopped the inflation at the pressure-pain tolerance and the corresponding VAS-score was determined (pressure-pain limit). The pressure at which VAS firstly exceeded 0 was defined as the pressure-pain threshold. Other disease markers (FM only): Isokinetic knee muscle strength, tenderpoint-count, myalgic score, Beck Depression Inventory, and Fibromyalgia Impact Questionnaire. Student's T-test was used to compare pressure-pain threshold and pressure-pain tolerance and the Mann-Whitney test to compare pressure-pain limit. Pearson's correlation was used to detect linear relationships. Pressure-pain threshold and pressure-pain tolerance assessed by CPA were significantly lower in FM compared to healthy controls. There was no difference in pressure-pain limit. CPA-parameters were significantly correlated to isokinetic muscle strength where more hypersensitivity resulted in lower strength. Pressure-pain threshold and pressure-pain tolerance assessed by CPA were significantly lower in patients with FM indicating muscle hyperalgesia. CPA was associated with knee muscle strength but not with measures thought to be influenced by psychological distress and mood.

Generalized deep-tissue hyperalgesia in patients with chronic low-back pain.

Some chronic painful conditions including e.g. fibromyalgia, whiplash associated disorders, endometriosis, and irritable bowel syndrome are associated with generalized musculoskeletal hyperalgesia. The aim of the present study was to determine whether generalized deep-tissue hyperalgesia could be demonstrated in a group of patients with chronic low-back pain with intervertebral disc herniation. Twelve patients with MRI confirmed lumbar intervertebral disc herniation and 12 age and sex matched controls were included. Subjects were exposed to quantitative nociceptive stimuli to the infraspinatus and anterior tibialis muscles. Mechanical pressure (thresholds and supra-threshold) and injection of hypertonic saline (pain intensity, duration, distribution) were used. Pain intensity to experimental stimuli was assessed on a visual analogue scale (VAS). Patients demonstrated significantly higher pain intensity (VAS), duration, and larger areas of pain referral following saline injection in both infraspinatus and tibialis anterior. The patients rated significantly higher pain intensity to supra-threshold mechanical pressure stimulation in both muscles. In patients, the pressure pain-threshold was lower in the anterior tibialis muscle compared to controls. In conclusion, generalized deep-tissue hyperalgesia was demonstrated in chronic low-back pain patients with radiating pain and MRI confirmed intervertebral disc herniation, suggesting that this central sensitization should also be addressed in the pain management regimes.

Central sensitization in fibromyalgia and other musculoskeletal disorders.

Muscle hyperalgesia and referred pain play an important role in chronic musculoskeletal pain. New knowledge on the involved basic mechanisms and better methods to assess muscle pain in the clinic are needed to revise and optimize treatment regimens. Increased muscle sensitivity is manifested as pain evoked by a normally non-nociceptive stimulus (allodynia), increased pain intensity evoked by nociceptive stimuli (hyperalgesia), or increased referred pain areas with associated somatosensory changes. Some manifestations of sensitization, such as expanded referred muscle pain areas in patients with chronic musculoskeletal pain, can be explained from animal experiments showing extrasegmental spread of sensitization. An important part of the pain manifestations (eg, tenderness and referred pain) related to chronic musculoskeletal disorders may result from peripheral and central sensitization, which may play a role in the transition from acute to chronic pain.