Non-inflammatory Muscle Pain Research Articles

A role for substance P and acid-sensing ion channel 1a in prolotherapy with dextrose-mediated analgesia in a mouse model of chronic muscle pain.

Prolotherapy is widely used in pain control and tissue repair in pain medicine. The classical mode is injection with hypertonic dextrose in muscle or perimysium. However, the analgesic mechanism is still not known. Here, we successfully established dextrose-mediated antinociception in a mouse model of fibromyalgia. The antinociceptive effects of dextrose injections were evaluated in a mouse model of fibromyalgia, in which bilateral chronic mechanical hyperalgesia was induced by unilateral intramuscular acid injection. The injectant (dextrose), dose (≥5%), and volume (>10 μL), but not osmolarity, were essential for the prolotherapy. Further studies showed that the activation of acid-sensing ion channel 1a (ASIC1a), neural activation, and the release of substance P from muscle afferents were required in the dextrose-induced reduction of mechanical hypersensitivity. Both pharmacological blockade and genetic deletion of ASIC1a or substance P as well as lidocaine abolished the dextrose-induced antinociception in mice with chronic hyperalgesia. Moreover, intramuscular dextrose injection induced phosphorylated extracellular signal-regulated kinase expression in dorsal root ganglion neurons expressing substance P; the phosphorylated extracellular signal-regulated kinase expression was inhibited by the ASIC1a antagonist PcTx1. The optimal settings for prolotherapy in fibromyalgia-like pain are dextrose dependent and volume dependent, and the peripheral antinociception involves ASIC1a and substance P signaling in muscle afferents. This study suggests a possible mechanism of action of dextrose prolotherapy in noninflammatory muscle pain such as fibromyalgia and provides insights into treating other types of chronic pain.

(−)-linalool-Loaded Polymeric Nanocapsules Are a Potential Candidate to Fibromyalgia Treatment

Fibromyalgia (FM) is a chronic disease that has as main characteristic generalized musculoskeletal pain, which can cause physical and emotional problems to patients. However, pharmacological therapies show side effects that hamper the adhesion to treatment. Given this, (-)-linalool (LIN), a monoterpene with several therapeutic properties already reported in scientific literature as anti-depressive, antinociceptive, anti-inflammatory, and antihyperalgesic also demonstrated therapeutic potential in the treatment of FM. Nevertheless, physicochemical limitations as high volatilization and poor water-solubility make its use difficult. In this perspective, this present research had performed the incorporation of LIN into polymeric nanocapsules (LIN-NC). Size, morphology, encapsulation efficiency, cytotoxicity, and drug release were performed. The antihyperalgesic effect of LIN-NC was evaluated by a chronic non-inflammatory muscle pain model. The results demonstrated that the polymeric nanocapsules showed particle size of 199.1 ± 0.7nm with a PDI measurement of 0.13 ± 0.01. The drug content and encapsulation efficiency were 13.78 ± 0.05mg/mL and 80.98 ± 0.003%, respectively. The formulation did not show cytotoxicity on J774 macrophages. The oral treatment with LIN-NC and free-LIN increased the mechanical withdrawal threshold on all days of treatment in comparison with the control group. In conclusion, LIN-NC is a promising proposal in the development of phytotherapy-based nanoformulations for future clinical applications.

Transcutaneous electrical nerve stimulation, acupuncture, and spinal cord stimulation on neuropathic, inflammatory and, non-inflammatory pain in rat models.

BackgroundTranscutaneous electrical nerve stimulation (TENS), manual acupuncture (MA), and spinal cord stimulation (SCS) are used to treat a variety of pain conditions. These non-pharmacological treatments are often thought to work through similar mechanisms, and thus should have similar effects for different types of pain. However, it is unclear if each of these treatments work equally well on each type of pain condition. The purpose of this study was to compared the effects of TENS, MA, and SCS on neuropathic, inflammatory, and non-inflammatory pain models.MethodsTENS 60 Hz, 200 μs, 90% motor threshold (MT), SCS was applied at 60 Hz, an intensity of 90% MT, and a 0.25 ms pulse width. MA was performed by inserting a stainless-steel needle to a depth of about 4-5 mm at the Sanyinjiao (SP6) and Zusanli (ST36) acupoints on a spared nerve injury (SNI), knee joint inflammation (3% carrageenan), and non-inflammatory muscle pain (intramuscular pH 4.0 injections) in rats. Mechanical withdrawal thresholds of the paw, muscle, and/or joint were assessed before and after induction of the pain model, and daily before and after treatment.ResultsThe reduced withdrawal thresholds were significantly reversed by application of either TENS or SCS (P < 0.05). MA, on the other hand, increased the withdrawal threshold in animals with SNI and joint inflammation, but not chronic muscle pain.ConclusionsTENS and SCS produce similar effects in neuropathic, inflammatory and non-inflammatory muscle pain models while MA is only effective in inflammatory and neuropathic pain models.

Eplingiella fruticosa (Lamiaceae) essential oil complexed with β-cyclodextrin improves its anti-hyperalgesic effect in a chronic widespread non-inflammatory muscle pain animal model

Eplingiella fruticosa (Lamiaceae), formally known as Hyptis fruticosa, is an important aromatic medicinal herb used in folk medicine in northeastern Brazil. We aimed to evaluate the anti-hyperalgesic effect of essential oil obtained from E. fruticosa (HypEO) complexed with βCD (HypEO-βCD) in a chronic widespread non-inflammatory muscle pain animal model (a mice fibromyalgia-like model, FM). The HypEO was extracted by hydro distillation and its chemical composition was determined by GC-MS/FID. Moreover, Fos protein expression in the spinal cord was assessed by immunofluorescence. (E)-caryophyllene, bicyclogermacrene, 1,8-cineole, α-pinene, β-pinene and 21 other compounds were identified in the HypEO. The treatment with HypEO-βCD produced a longer-lasting anti-hyperalgesic effect compared to HypEO, without alterations in motor coordination or myorelaxant effects. Moreover, HypEO and HypEO-βCD produced a significant anti-hyperalgesic effect over 7 consecutive treatment days. Immunofluorescence assay demonstrated a decrease in Fos protein expression in the spinal cord (p < 0.001). We demonstrated that the anti-hyperalgesic effect produced by HypEO was improved after complexation with β-CD and this seems to be related to the central pain-inhibitory pathway, suggesting the possible use of E. fruticosa for chronic pain management.

Chronic non-inflammatory muscle pain: central and peripheral mediators

Conditions with chronic widespread non-inflammatory muscle pain, such as fibromyalgia, have complex etiologies with numerous proposed mechanisms for their pathophysiology of underlying chronic pain. Advancements in neuroimaging have allowed for the study of brain function and connectivity in humans with these conditions, while development of animal models have allowed for the study of both peripheral and central factors that lead to chronic pain. This article reviews the current literature surrounding the pathophysiology of chronic widespread non-inflammatory muscle pain focusing on both peripheral and central nervous system, as well as immune system, contributions to the development and maintenance of pain. A better understanding of the mechanisms underlying these conditions can allow for improvements in patient education, treatment and outcomes.

Dynamic expression of glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 in the mouse spinal cord dorsal horn under pathological pain states

ABSTRACTObjective: Animal models of chronic pain have demonstrated that glial cells are promising target for development of analgesic drugs. However, preclinical studies on glial response under chronic pain conditions vary depending on the cellular markers, the species used, the experimental design and model. Therefore, we investigate the expression profile of GFAP and Iba-1 during the behavioral manifestation of sensory disorder in inflammatory and neuropathic pain models.Methods: the expression profile of fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule-1 (Iba-1) were quantitated in the spinal dorsal horn of Balb/C mice submitted to six models of chronic pain. Protein analysis was performed by western blot and the results colligated with pain-related behavior.Results: Using the same method to quantitate proteins we observed that while GFAP is upregulated after axotomy, partial nerve injury and cutaneous inflammation, its expression is not changed during muscle inflammation, non-inflammatory muscle pain, and in a viral-associated pain. Differently, Iba-1 is downregulated after axotomy but upregulated after partial lesion of peripheral nerve as well as after virus inoculation and during non-inflammatory muscle pain. Cutaneous and muscle inflammation induced no change in Iba-1 expression in the dorsal horn.In spite of a marked time-dependent variation in protein expression, mechanical allodynia was present at any time of all the models investigated.Discussion: Under distinct pain conditions, GFAP and Iba-1 expression is dependent on the origin of the stimulus, disease progression and tissue affected. Moreover, their expression and is not necessarily associated to the behavior manifestation of pain.

Resident Macrophages in Muscle Contribute to Development of Hyperalgesia in a Mouse Model of Noninflammatory Muscle Pain.

Macrophages play a role in innate immunity within the body, are located in muscle tissue, and can release inflammatory cytokines that sensitize local nociceptors. In this study we investigate the role of resident macrophages in the noninflammatory muscle pain model induced by 2 pH 4.0 preservative-free sterile saline (pH 4.0) injections 5days apart in the gastrocnemius muscle. We showed that injecting 2 pH 4.0 injections into the gastrocnemius muscle increased the number of local muscle macrophages, and depleting muscle macrophages with clodronate liposomes before acid injections attenuated the hyperalgesia produced by this model. To further examine the contribution of local macrophages to this hyperalgesia, we injected mice intramuscularly with C34, a toll-like receptor 4 (TLR4) antagonist. When given before the first pH 4.0 injection, C34 attenuated the muscle and tactile hyperalgesia produced by the model. However, when given before the second injection C34 had no effect on the development of hyperalgesia. Then to test whether activation of local macrophages sensitizes nociceptors to normally non-nociceptive stimuli we replaced either the first or second acid injection with the immune cell activator lipopolysaccharide, or the inflammatory cytokine interleukin (IL)-6. Injecting LPS or IL-6 instead of the either the first or second pH 4.0 injection resulted in a dose-dependent increase in paw withdrawal responses and decrease in muscle withdrawal thresholds. The highest doses of LPS and IL-6 resulted in development of hyperalgesia bilaterally. The present study showed that resident macrophages in muscle are key to development of chronic muscle pain. This article presents evidence for the role of macrophages in the development of chronic muscle pain using a mouse model. These data suggest that macrophages could be a potential therapeutic target to prevent transition of acute to chronic muscle pain particularly in tissue acidosis conditions.

Ocimum basilicum essential oil complexed with β‐Cyclodextrin increases fos protein expression in CNS areas and produces analgesic profile

Ocimum basilicum leaves essential oil (LEO) is rich in monoterpenes, such as linalool and geraniol, and it have shown analgesic effects, but short half‐life and water insolubility are restraint for LEO therapeutic approaches. β‐cyclodextrin (β‐CD) has been applied to improve pharmacological profiles of essential oils or related compounds. Thus, we assessed the antihiperalgesic effect of LEO, alone, or complexed in β‐CD (LEO/β‐CD), on chronic non‐inflammatory muscle pain (an animal model for fibromyalgia) and evaluate the c‐Fos expression in the mice CNS). Mice were treated every day with either LEO/β‐CD (25, 50 or 100 mg/kg, p.o.), LEO (25 mg /kg, p.o.), tramadol (TRM 4mg /kg, i.p.) or vehicle (saline), and 60 minutes after treatment parameters were assessed. Oral treatment with LEO or LEO‐βCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia (p&lt;0.001) and they are able to significantly (p&lt;0.05) increase Fos protein expression in nucleus raphe magnus and periaqueductal gray. Our results provide evidence suggesting that LEO and LEO/β‐CD produces analgesic effects through an activation of CNS areas, such as periaqueductal grey.Financial Support: CNPq/Brazil, CAPES/Brazil, FAPITEC/SE/Brazil and FINEP/Brazil

Spinal cord stimulation reduces mechanical hyperalgesia and restores physical activity levels in animals with noninflammatory muscle pain in a frequency-dependent manner.

Spinal cord stimulation (SCS) is an effective treatment for neuropathic pain, but its effect on chronic muscle pain is unclear. We designed this study to test the effect of SCS in an animal model of noninflammatory muscle pain. Male Sprague-Dawley rats were implanted with an epidural SCS lead on the upper lumbar spinal cord (L3-L4) under isoflurane anesthesia (4%). Ten days after implantation, chronic muscle pain was induced by giving 2 injections of pH 4 saline into the left gastrocnemius muscle, 5 days apart. In experiment 1, SCS was delivered daily (6-hour duration/day) for 4 days at one of 4 different frequencies (0 (sham), 4, 60, and 100 Hz) from day 6 to day 9. Paw withdrawal threshold and muscle withdrawal threshold were measured before the first injection, and before and during SCS daily. Physical activity (distance, crossing, stand, and grooming) was assessed before the first injection, before SCS on day 6 and during SCS on day 9. In experiment 2, SCS was delivered (6 hours) on day 6 at either 60 or 100 Hz. Paw withdrawal threshold and muscle withdrawal threshold were assessed before the first injection, before and during SCS on day 6, and daily for the following 3 days (day 7-day 9). Paw withdrawal threshold and muscle withdrawal threshold significantly decreased bilaterally after the second injection of acidic saline. SCS delivered at 60 or 100 Hz significantly reversed the decreased paw withdrawal threshold and muscle withdrawal threshold bilaterally when compared with that of sham SCS, but 4 Hz SCS had no effect on paw withdrawal threshold and muscle withdrawal threshold. SCS (60 or 100 Hz) delivered daily provided a persistently reversed effect, and SCS delivered singly provided a carryover effect for 24 hours. During 60 Hz SCS, the distance traveled and the number of crossings increased significantly when compared with that of sham SCS. The current study shows that higher frequencies of SCS (60 and 100 Hz) significantly reduce mechanical hyperalgesia of the paw and muscle in an animal model of noninflammatory muscle pain, and 60 Hz SCS restores physical activity levels of animals, not 4 Hz.

Linalool and linalool complexed in β-cyclodextrin produce anti-hyperalgesic activity and increase Fos protein expression in animal model for fibromyalgia

The analgesic activity of (-)-linalool (LIN), a monoterpene present in essential oils of Lamiaceae species, has been previously demonstrated in rodents. However, its possible use in the treatment of fibromyalgia (FM) was never demonstrated. Additionally, as a short half-life is a limitation for the LIN medicinal application, the employment of drug delivery systems has been used to improve pharmaceutical properties of this compound. We investigated the anti-nociceptive effect of LIN, isolated or in β-cyclodextrin complex (LIN-CD), in an animal model of chronic non-inflammatory muscle pain (a FM animal model), as well as its effect on the central nervous system (CNS). Male Swiss mice were subjected to two injections of acidic saline (pH 4; 20μL/gastrocnemius) and were treated on alternate days, with LIN-CD (25mg/kg, p.o.), LIN (25mg/kg, p.o.), tramadol (TRM 4mg/kg, i.p.), or vehicle (neutral saline). After 60min, they were screened for mechanical hyperalgesia (von Frey), motor coordination (rotarod), and muscle strength (grip strength meter) for 27days. The CNS areas involved in the anti-hyperalgesic activity were evaluated by immunofluorescence. LIN or LIN-CD produced a significant reduction (p < 0.001) of mechanical hyperalgesia on chronic non-inflammatory muscle pain model, which remained for 24h only in LIN-CD, and these compounds significantly (p < 0.05) activated neurons of the locus coeruleus, nucleus raphe magnus, and periaqueductal gray areas. So, our results suggest that LIN-CD improved analgesic profile of LIN, with a probable involvement of descending pain pathways and the anti-nociceptive effect of linalool in an animal model of chronic non-inflammatory muscle pain. So far, only the investigations in animal models of inflammatory pain and supraspinatus were published.

(376) Spinal cord stimulation reduces mechanical hyperalgesia and restores physical activity levels in animals with non-inflammatory muscle pain in a frequency-dependent manner

Chronic musculoskeletal pain (CMP) conditions have a strong central component to their pain, and are associated with significant pain and disability that is difficult to treat. The current study tested the effects of SCS in an animal model of chronic muscle pain that mimics the symptoms of CMP. Ten days after an epidural SCS lead was implanted into the spinal cord (L3-L4) of Sprague-Dawley rats, chronic muscle pain was induced by two injections of pH 4 saline into one gastrocnemius muscle, 5 days apart.

Assessment of avoidance behaviors in mouse models of muscle pain

Pain encompasses both a sensory as well as an affective dimension and these are differentially processed in the cortex. Animal models typically use reflexive behaviors to test nociceptive responses; these are thought to reflect the sensory dimension of pain. While several behavioral tests are available for examining the affective dimension of pain it is unclear if these are appropriate in animal models of muscle pain. We therefore tested the utility of existing paradigms as well as new avoidance paradigms in animal models of muscle pain in mice. Specifically we used an escape-avoidance test to noxious mechanical stimuli, a learned avoidance test to noxious mechanical stimuli, and avoidance of physical activity. We used three animal models of muscle pain: carrageenan-induced inflammation, non-inflammatory muscle pain, and exercise-enhanced pain. In the carrageenan model of inflammation mice developed escape-avoidance behaviors to mechanical stimuli, learned avoidance to mechanical stimulation and avoidance of physical activity – these models are associated with unilateral hyperalgesia. When both muscles were inflamed, escape-avoidance behaviors did not develop suggesting that equivalent bilateral pain behaviors cannot be tested with an escape-avoidance test. In the non-inflammatory muscle pain model mice did not show significant changes in escape-avoidance behaviors or learned avoidance, but did avoid physical activity. In the exercise-enhanced pain model, there were no changes in escape-avoidance, learned avoidance of noxious or physical activity In conclusion, we developed several testing protocols that assess supraspinal processing of pain behaviors in models of muscle pain and that are most sensitive in animals with unilateral hyperalgesia.

The place escape/avoidance paradigm: A novel method to assess nociceptive processing

This paper summarizes a behavioral paradigm that was developed as a novel method to dissociate the multidimensional pain experience in rodents. The place escape/avoidance paradigm (PEAP) is based on the assumption that if animals escape and/or avoid a noxious stimulus, then the stimulus is aversive to the animal. Data is presented showing that when animals are placed in a specific environmental condition, they will perform purposeful behavior to escape and/or avoid the noxious stimulus. Additional data is presented to demonstrate the validity of the behavioral paradigm and how the paradigm has been used to test the hypothesis that the affective/motivational dimension of pain can be dissociated and studied independent of sensory pain processing. The behavioral paradigm highlights the emerging trend in the area of pain research and management towards developing more realistic behavioral paradigms to assess nociceptive processing in rodent models of chronic pain.

Electrical stimulation reduces secondary mechanical hyperalgesia in a non-inflammatory pain model in rats

Fibromyalgia is a musculoskeletal disease characterized by widespread pain. Its physiological mechanisms are not clear yet, which directly interferes on the quality of pain management. Electrical therapeutic approaches such as interferential current (IFC) and transcutaneous electrical nerve stimulation (TENS) have been used in several pain conditions. To our knowledge this is the first study investigating the effects of both IFC and TENS on reduction of secondary mechanical hyperalgesia in a non-inflammatory muscle pain models in rats. Double intramuscular injection of acid saline (Ph 4.0) was performed five days apart on the left gastrocnemius muscle. Twenty male Wistar rats were divided in four groups: high frequency TENS (100Hz), low frequency TENS (5Hz), interferential current-IFC (modulated frequency of 100Hz) and sham stimulation. Control animals received the same treatment but with no delivery of electrical stimulation. A pair of round electrodes were placed at the lateral and medial aspects of the left gastrocnemius muscle. Animals were lightly anesthetized (5%-2%) with isoflurane and received a single stimulation for 20 minutes. Sensorial intensity was set for starting stimulation. Mechanical hyperalgesia was assessed through von Frey filaments with increasing bending forces before both first and second acid saline injections, 24 h after second injection and following the treatment. All animals showed significant reduction of the mechanical hyperalgesia 24 h after the second injection (p< 0.05). There was a significant reduction of the mechanical hyperalgesia in IFC-treated (p< 0.01) and both high and low frequency TENS-treated animals (p<0,03) compared to sham animals. Thus we suggest that both IFC and TENS at both high and low frequencies promote antinociceptive effect on muscle pain model. Fibromyalgia is a musculoskeletal disease characterized by widespread pain. Its physiological mechanisms are not clear yet, which directly interferes on the quality of pain management. Electrical therapeutic approaches such as interferential current (IFC) and transcutaneous electrical nerve stimulation (TENS) have been used in several pain conditions. To our knowledge this is the first study investigating the effects of both IFC and TENS on reduction of secondary mechanical hyperalgesia in a non-inflammatory muscle pain models in rats. Double intramuscular injection of acid saline (Ph 4.0) was performed five days apart on the left gastrocnemius muscle. Twenty male Wistar rats were divided in four groups: high frequency TENS (100Hz), low frequency TENS (5Hz), interferential current-IFC (modulated frequency of 100Hz) and sham stimulation. Control animals received the same treatment but with no delivery of electrical stimulation. A pair of round electrodes were placed at the lateral and medial aspects of the left gastrocnemius muscle. Animals were lightly anesthetized (5%-2%) with isoflurane and received a single stimulation for 20 minutes. Sensorial intensity was set for starting stimulation. Mechanical hyperalgesia was assessed through von Frey filaments with increasing bending forces before both first and second acid saline injections, 24 h after second injection and following the treatment. All animals showed significant reduction of the mechanical hyperalgesia 24 h after the second injection (p< 0.05). There was a significant reduction of the mechanical hyperalgesia in IFC-treated (p< 0.01) and both high and low frequency TENS-treated animals (p<0,03) compared to sham animals. Thus we suggest that both IFC and TENS at both high and low frequencies promote antinociceptive effect on muscle pain model.

Activation of NMDA Receptors in the Brainstem, Rostral Ventromedial Medulla, and Nucleus Reticularis Gigantocellularis Mediates Mechanical Hyperalgesia Produced by Repeated Intramuscular Injections of Acidic Saline in Rats

Repeated injections of acidic saline into the gastrocnemius muscle induce both muscle and cutaneous hypersensitivity. We have previously shown that microinjection of local anesthetic into either the rostral ventromedial medulla (RVM) or the nucleus reticularis gigantocellularis (NGC) reverses this muscle and cutaneous hypersensitivity. Although prior studies show that NMDA receptors in the RVM play a clear role in mediating visceral and inflammatory hypersensitivity, the role of NMDA receptors in the NGC or in noninflammatory muscle pain is unclear. Therefore, the present study evaluated involvement of the NMDA receptors in the RVM and NGC in muscle and cutaneous hypersensitivity induced by repeated intramuscular injections of acidic saline. Repeated intramuscular injections of acidic saline, 5 days apart, resulted in a bilateral decrease in the withdrawal thresholds of the paw and muscle in all groups 24 hours after the second injection. Microinjection of NMDA receptor antagonists into the RVM reversed both the muscle and cutaneous hypersensitivity. However, microinjection of NMDA receptor antagonists into the NGC only reversed cutaneous but not muscle hypersensitivity. These results suggest that NMDA receptors in the RVM mediate both muscle and cutaneous hypersensitivity, but those in the NGC mediate only cutaneous hypersensitivity after muscle insult. The current study shows that NMDA receptors in supraspinal facilitatory sites maintain noninflammatory muscle pain. Clinical studies in people with chronic widespread, noninflammatory pain, similarly, show alterations in central excitability. Thus, understanding mechanisms in an animal model could lead to improved treatment for patients with chronic muscle pain.

Central mechanisms in the maintenance of chronic widespread noninflammatory muscle pain.

Chronic widespread pain (CWP) conditions such as fibromyalgia and myofascial syndromes are characterized by generalized pain, tenderness, morning stiffness, disturbed sleep, and pronounced fatigue. However, CWP pathophysiology is still unclear. A number of hypotheses have been proposed as the underlying pathophysiology of CWP: muscular dysfunction/ischemia, central sensitization, and a deficit in endogenous pain-modulating systems. This article reviews the current and emerging literature about the pathophysiology and neurobiology of chronic widespread -musculoskeletal pain. Widespread musculoskeletal pain results in changes in the central nervous system in human subjects and animal models. These changes likely reflect alterations in supraspinal modulation of nociception, and include increases in excitatory and decreases in inhibitory modulation pathways. These alterations in excitation and inhibition likely drive changes observed in the spinal cord to result in central sensitization, and the consequent pain and hyperalgesia.

The Role of Peripheral Glutamate and Glutamate Receptors in Muscle Pain

Objectives: To review evidence that associates elevated muscle interstitial glutamate concentration and the activation of peripheral glutamate receptors with the development and maintenance of muscle pain in conditions such as myofascial temporomandibular disorders [TMDs].Findings: In certain noninflammatory musculoskeletal pain conditions, an association between pain, elevated glutamate concentrations and the expression of peripheral N-methyl-d-aspartate receptors [NRs] has been made. Myofascial TMDs are a noninflammatory muscle pain disorder characterized by pain and localized mechanical sensitivity in the masticatory muscle and a greater prevalence in young women than in men. Artificial elevation of glutamate concentrations in the masticatory muscles of healthy subjects evokes intense, short duration pain that is significantly greater in woman than in men and induces a more prolonged, localized mechanical sensitization that is similar in both sexes. Glutamate-evoked pain and sensitization may be attenu...

Pregabalin reduces primary and secondary hyperalgesia in a rat model of chronic non-inflammatory muscle pain

Pregabalin reduces primary and secondary hyperalgesia in a rat model of chronic non-inflammatory muscle pain