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Preclinical assessment of pain has typically relied on measuring animal responses to evoked stimulation. Because of inherent limitations of these assays, there is a need to develop measures of animal pain/discomfort that are objective, not experimentally evoked, and mimic the human condition. Patients with chronic pain manifest a variety of co-morbidities, one of which is disturbances in sleep. We...
Understanding deep muscle pain is of increasing importance for evaluating clinical pathologic pain states. Previously, a central role of deep muscle tissue in the development of ongoing pain behavior after incision was demonstrated. The underlying mechanisms, however, remain unclear. Using a new in vitro plantar flexor digitorum brevis (FDB) muscle–nerve preparation, we investigated properties of...
Surgery injures both skin and deep tissue causing pain at rest and evoked pain with activities. In this study, we examined the extent of injury by incision and dorsal horn neuron (DHN) spontaneous activity (SA) in rats that underwent a sham operation, skin incision or skin plus deep tissue incision. Pain behaviors were measured 1day later followed by DHN recordings in the same rats. On postoperative...
We examined nociceptive responses to mechanical stimulation in mice of both sexes lacking the estrogen receptor α or β and in respective wild types under normal conditions, after inflammation of a hindpaw or peripheral nerve injury. In normal wild-type mice, females had significantly lower paw withdrawal threshold than males. There was no significant difference between wild-type mice and knock-outs...
Functional magnetic resonance imaging (fMRI) has been used to map cerebral activations related to nociceptive stimuli in rodents. Here, we used fMRI to investigate abnormally increased responses to noxious or innocuous stimuli, in a well-established rat model of chronic neuropathic pain induced by photochemical lumbar spinal cord injury. In this model, a subpopulation of rats exhibits allodynia-like...
Neuropathic pain is a common consequence of damage to the nervous system. We here report a genetic analysis of development of neuropathic pain-like behaviors after unilateral photochemically-induced ischemic sciatic nerve injury in a panel of inbred rat strains known to display different susceptibility to autoimmune neuroinflammation. Pain behavior was initially characterized in Dark-Agouti (DA; RT1...
We used a photochemical method to generate a partial ischemic injury to the infraorbital branch of the trigeminal nerve in rats. Following injury, rats developed a bilateral persistent hypersensitivity to mechanical stimulation in the territory innervated by the infraorbital nerve. In addition, spread of mechanical hypersensitivity beyond the facial region was noted. Heat hypersensitivity was also...
Controversy persists in relation to the analgesic efficacy of opioids in neuropathic pain. In the present study the effects of acute, subcutaneous administration of the μ-opioid receptor agonists morphine, methadone and codeine were examined in rat models of peripheral and central neuropathic pain. In the spared nerve injury (SNI) and chronic constriction injury (CCI) models of peripheral neuropathic...
The role of the adenosine A 1 receptor in nociception was assessed using mice lacking the A 1 receptor (A 1 R−/−) and in rats. Under normal conditions, the A 1 R−/− mice exhibited moderate heat hyperalgesia in comparison to the wild-type mice (A 1 R+/+). The mechanical and cold sensitivity were unchanged. The antinociceptive effect of morphine given intrathecally...
The development of tolerance to chronically administered methadone and morphine was examined in a rat model of neuropathic pain after ischemic nerve injury. In drug naive neuropathic rats systemically administered morphine or methadone similarly and dose-dependently alleviated mechanical allodynia. Tolerance to the anti-hyperalgesic effect of equally effective doses of morphine (10mg/kg) or methadone...
The development of neuropathic-like behaviors following unilateral ischemic injury to the sciatic nerve was examined and compared in four rat strains: Sprague-Dawley (SD), Wistar--Kyoto (WK), spontaneously hypertensive (SHR) and Dark-Agouti (DA). We have also compared two sub-strains of SD rats supplied from two different vendors (SD-BK and SD-DK). The responses to mechanical, heat or cold stimuli...
The present study assessed the effect of a single subcutaneous injection of resiniferatoxin (RTX), an ultrapotent capsaicin analogue, on the activity of spinal cholecystokinin (CCK) systems, by using electrophysiological and in situ hybridization techniques. Subcutaneous RTX at 0.3 mg/kg, but not vehicle, produced marked thermal hypoalgesia in rats on the hot plate and tail flick tests. Partial recovery...
We examined the effects of intrathecal nociceptin, the endogenous ligand for the orphan opioid receptor-like receptor, on abnormal pain-related behaviors in rats after carrageenan-induced inflammation and photochemically-induced peripheral nerve or spinal cord ischemic injury. Intrathecal nociceptin dose-dependently alleviated mechanical and cold allodynia-like behavior in the two models of neuropathic...
We have previously reported that we have observed chronic pain-like response to light mechanical stimuli (allodynia) in rats after severe spinal cord ischemia, which resembles some painful conditions in chronic spinally injured patients and is not relieved by a number of conventional analgesics used for treating chronic neuropathic pain. In the present study, we tested the effects of the non-selective...
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