Atsuko Morimoto

Two-week cast immobilization induced chronic widespread hyperalgesia in rats.

It has been postulated that physical immobilization is an essential factor in developing chronic pain after trauma or surgery in an extremity. However, the mechanisms of sustained immobilization‐induced chronic pain remain poorly understood. The present study, therefore, aimed to develop a rat model for chronic post‐cast pain (CPCP) and to clarify the mechanism(s) underlying CPCP. To investigate the effects of cast immobilization on pain behaviours in rats, one hindlimb was immobilized for 2 weeks with a cast and remobilization was conducted for 10 weeks. Cast immobilization induced muscle atrophy and inflammatory changes in the immobilized hindlimb that began 2 h after cast removal and continued for 1 week. Spontaneous pain‐related behaviours (licking and reduction in weight bearing) in the immobilized hindlimb were observed for 2 weeks, and widespread mechanical hyperalgesia in bilateral calves, hindpaws and tail all continued for 5–10 weeks after cast removal. A sciatic nerve block with lidocaine 24 h after cast removal transitorily abolished bilateral mechanical hyperalgesia in CPCP rats, suggesting that sensory inputs originating in the immobilized hindlimb contribute to the mechanism of both ipsilateral and contralateral hyperalgesia. Intraperitoneal injection of the free radical scavengers 4‐hydroxy‐2,2,6,6‐tetramethylpiperydine‐1‐oxy1 or N‐acetylcysteine 24 h after cast removal clearly inhibited mechanical hyperalgesia in bilateral calves and hindpaws in CPCP rats. These results suggest that cast immobilization induces ischaemia/reperfusion injury in the hindlimb and consequent production of oxygen free radicals, which may be involved in the mechanism of widespread hyperalgesia in CPCP rats.

Treadmill running and static stretching improve long-lasting hyperalgesia, joint limitation, and muscle atrophy induced by cast immobilization in rats

The effects of exercise on chronic pain induced by immobilization are incompletely understood. The purpose of this study was to investigate whether 30min of treadmill running (TR; active exercise) and 10min of static stretching (SS; passive exercise) of the immobilized hindlimb reduce widespread chronic pain, joint limitation, and hindlimb muscle atrophy induced by cast immobilization in rats. One hindlimb of Sprague Dawley (SD) rats was immobilized for 2 weeks with a cast, and remobilization was conducted for 7 weeks. MRI study showed that cast immobilization had induced inflammatory changes in the immobilized hindlimb, beginning as early as 2h after cast removal; these changes continued for 2-3 days. Mechanical hyperalgesia in the calf and hindpaw developed as early as 2h after cast removal and continued for 7 weeks. TR and SS were initiated 3 days after cast removal and were continued 3 times per week for 2 weeks. Both forms of exercise significantly inhibited mechanical hyperalgesia in the calf and hindpaw in immobilized rats. Range-of-motion limitations in the knee and ankle joints and calf muscle atrophy after cast removal were also decreased by both TR and SS. This study is the first to demonstrate the beneficial effect of TR and SS on widespread chronic pain, joint limitation, and muscle atrophy in a cast-immobilized rat model.

Associations Between Pain drawing and Psychological Characteristics of Different Body Region Pains

Pain drawings have frequently been used for documentation of pain and a convenient diagnosis tool. Pain drawings were found to be associated with psychological states in chronic patients with low back pain. Few researchers have investigated pain drawings except in low back pain. The aim of this study was to investigate the pain, pain drawings, psychological characteristics, and pain interference in the head, neck–shoulder (NS), and low‐back/lower‐limb (LB‐LL) regions among patients with chronic pain.

The Effects of Exercise Therapy for the Improvement of Jaw Movement and Psychological Intervention to Reduce Parafunctional Activities on Chronic Pain in the Craniocervical Region

Apparent organic abnormalities are sometimes not identified among patients suffering from chronic pain in the craniocervical region. In some cases, parafunctional activities (PAs) are recognized. PAs are nonfunctional oromandibular activities that include jaw clenching and bruxism, but are considered as factors that contribute to craniomandibular disorders (CMDs). It is now recognized that PAs and CMDs influence musculoskeletal conditions of the upper quarter. Exercise therapy (ET) to improve jaw movement and psychological intervention (PI) to reduce PAs are useful for PAs and CMDs. We hypothesized that ET and PI would be effective for craniocervical pain without organic abnormalities.

Activated spinal astrocytes are involved in the maintenance of chronic widespread mechanical hyperalgesia after cast immobilization

BackgroundIn the present study, we examined spinal glial cell activation as a central nervous system mechanism of widespread mechanical hyperalgesia in rats that experienced chronic post-cast pain (CPCP) 2 weeks after cast immobilization. Activated spinal microglia and astrocytes were investigated immunohistologically in lumbar and coccygeal spinal cord segments 1 day, 5 weeks, and 13 weeks following cast removal.ResultsIn the lumbar cord, astrocytes were activated after microglia. Astrocytes also were activated after microglia in the coccygeal cord, but with a delay that was longer than that observed in the lumbar cord. This activation pattern paralleled the observation that mechanical hyperalgesia occurred in the hindleg or the hindpaw before the tail. The activating transcription factor 3 (ATF3) immune response in dorsal root ganglia (DRG) on the last day of cast immobilization suggested that nerve damage might not occur in CPCP rats. The neural activation assessed by the phosphorylated extracellular signal-regulated kinase (pERK) immune response in DRG arose 1 day after cast removal. In addition, L-α-aminoadipate (L-α-AA), an inhibitor of astrocyte activation administered intrathecally 5 weeks after cast removal, inhibited mechanical hyperalgesia in several body parts including the lower leg skin and muscles bilaterally, hindpaws, and tail.ConclusionsThese findings suggest that activation of lumbar cord astrocytes is an important factor in widespread mechanical hyperalgesia in CPCP.

Low rather than high dose lipopolysaccharide ‘priming’ of muscle provides an animal model of persistent elevated mechanical sensitivity for the study of chronic pain

Experimental animal pain models involving peripheral nerve lesions have expanded the understanding of the pathological changes caused by nerve damage. However models for the pathogenesis of chronic pain patients lacking obvious nerve injuries have not been developed to the same extent. Guided by clinical observations, we focused on the initiating noxious event, the context when applying nociceptive stimulation targeting long‐lasting pain elicited by muscle insult. The administration of a nociceptive agent (6% hypertonic saline: HS; 5‐time repeated‐injection: HS5) after pretreatment with an immuno‐inflammatory agent (lipopolysaccharide: LPS, 2μg/kg) into one gastrocnemius muscle produced markedly long‐persisting biphasic sustained mechanical hypersensitivity on the plantar surface of both hindpaws. In the acute phase, the blockade of afferent inputs from the injected‐site was effective in returning the contralateral enhanced‐responses to baseline levels. In contrast, similar blockade during the chronic phase did not affect the contralateral enhanced‐responses, indicating that the hypersensitivity in the two phases was probably induced by different mechanisms. However, increasing the dose of LPS (20μg/kg) before applying HS5 eliminated the development of mechanical hypersensitivity in the chronic phase, while the hypersensitivity in the acute phase was significantly more severe than with low‐dose LPS‐pretreatment. In this model, the development of hypersensitivity could be modulated by manipulating LPS‐doses prior to noxious stimulation. This novel chronic pain model based on a preceding ‘priming’ myalgic stimulus provides an intriguing means for studying the pathogenesis of chronic pain.