Thermal hyperalgesia and mechanical allodynia produced by intrathecal administration of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein, gp120.
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.
Milligan
E D
ED
Department of Psychology, University of Colorado at Boulder, Campus Box 345, Boulder, CO 80309-0345, USA. emilligan@clipr.colorado.edu
Mehmert
K K
KK
Hinde
J L
JL
Harvey
L O
LO
Martin
D
D
Tracey
K J
KJ
Maier
S F
SF
Watkins
L R
LR
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D002951:Citrates / Q000627:therapeutic use; D015699:HIV Envelope Protein gp120 / Q000009:adverse effects*; D006358:Hot Temperature / Q000009:adverse effects; D006835:Hydrazones / Q000627:therapeutic use; D006930:Hyperalgesia / Q000139:chemically induced* / Q000188:drug therapy; D008297:Male; D009457:Neuroglia / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013116:Spinal Cord / Q000187:drug effects; D014110:Touch / Q000187:drug effects; D000813:Anilides; D006146:Guanidines
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002951:Citrates; D015699:HIV Envelope Protein gp120; D006835:Hydrazones; C007744:fluorocitrate; C097256:semapimod; D000813:Anilides; D006146:Guanidines