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 purpose of this study was to investigate the role of peripheral macrophages in the generation of mechanical allodynia utilizing a modification of the Chung rat model of neuropathy. Three distinct methods were used: (1) systemic and perineural macrophage inhibition utilizing CNI-1493; (2) depletion of the peripheral macrophage population by liposome-encapsulated clodronate; and (3) perineural administration of activated or inactivated bone marrow-derived macrophages (BMDM) in sham-surgery rats. Mechanical allodynia was tested on days 1, 3, 5, 7, and 10 post-intervention or surgery using von Frey monofilaments. In order to assess the role of spinal glia following these interventions, microglial (CNS macrophages) and astrocytic activation was assessed using immunohistochemistry. CNI-1493 did not attenuate mechanical allodynia, or spinal glial expression as compared to the saline control group. Similarly, the clodronate depletion of peripheral macrophages prior to nerve injury did not have any effect on the resultant mechanical allodynia or spinal glial activation. Perineural administration of activated or inactivated BMDM did not evoke mechanical allodynia in sham surgery rats. Of interest, we observed an ipsilateral, dorsal horn increase in microglial expression following perineural administration of activated macrophages. In summary, these data suggest a limited role of activated macrophages in the onset of mechanical allodynia in an animal model of neuropathy.
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PMID:Limited role of macrophages in generation of nerve injury-induced mechanical allodynia. 1115 May 54