Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162473 (Frey)
 2,599 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Astrocytes and microglia in the spinal cord have recently been reported to contribute to the development of peripheral inflammation-induced exaggerated pain states. Both lowering of thermal pain threshold (thermal hyperalgesia) and lowering of response threshold to light tactile stimuli (mechanical allodynia) have been reported. The notion that spinal cord glia are potential mediators of such effects is based on the disruption of these exaggerated pain states by drugs thought to preferentially affect glial function. Activation of astrocytes and microglia can release many of the same substances that are known to mediate thermal hyperalgesia and mechanical allodynia. The aim of the present series of studies was to determine whether exaggerated pain states could also be created in rats by direct, intraspinal immune activation of astrocytes and microglia. The immune stimulus used was peri-spinal (intrathecal, i.t.) application of the Human Immunodeficiency Virus type 1 (HIV-1) envelope glycoprotein, gp120. This portion of HIV-1 is known to bind to and activate microglia and astrocytes. Robust thermal hyperalgesia (tail-flick, TF, and Hargreaves tests) and mechanical allodynia (von Frey and touch-evoked agitation tests) were observed in response to i.t. gp120. Heat denaturing of the complex protein structure of gp120 blocked gp120-induced thermal hyperalgesia. Lastly, both thermal hyperalgesia and mechanical allodynia to i.t. gp120 were blocked by spinal pretreatment with drugs (fluorocitrate and CNI-1493) thought to preferentially disrupt glial function.
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PMID:Thermal hyperalgesia and mechanical allodynia produced by intrathecal administration of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein, gp120. 1075 70

The present study has assessed the efficacy and potency of systemic, intrathecal (i.t.) and intracerebroventricular (i.c.v.) morphine in alleviating a chronic mechanical allodynia-like behaviour in a rat model of central pain after spinal cord injury. The anti-allodynic potency of morphine was compared to its antinociceptive potency in both spinally injured and normal rats. Systemic (intraperitoneal or subcutaneous) morphine did not significantly relieve allodynia up to 3 mg/kg cumulative dose, which was sedative. Mechanical allodynia-like behaviour was only significantly relieved by l0 mg/kg morphine which caused severe sedation. Low doses of i.c.v. morphine abolished vocalization of allodynic rats to von Frey hair stimulation. However, other components of abnormal reactions to innocuous mechanical stimulation, such as agitation, jumping and avoidance, were only relieved by i.c.v. morphine at high, sedative doses. In contrast, i.t. morphine dose dependently reversed all components of the allodynic reactions without causing sedation. Morphine administered by all three routes produced powerful antinociception in the tail flick test in normal rats. The antinociceptive potency of morphine was reduced after systemic, i.t. and, particularly, i.c.v. administration in allodynic rats. These results indicated that i.t. morphine relieved the mechanical allodynia-like responses in spinally injured rats, whereas systemic or i.c.v. morphine only increased the response threshold to innocuous mechanical stimulation at high doses, which was associated with sedation, making it difficult to assess the anti-allodynic effect. However, i.c.v. morphine may be particularly effective for the affective component of pain in the present model. The antinociceptive potency of morphine was also reduced in spinally injured rats. It is suggested that morphine may be differentially effective against different types of pain after different routes of administration. Spinal morphine may be a therapeutic alternative in treating central pain after spinal cord injury.
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PMID:Comparison of the anti-allodynic and antinociceptive effects of systemic; intrathecal and intracerebroventricular morphine in a rat model of central neuropathic pain. 1510 25