Topical capsaicin-induced allodynia in unanesthetized primates: pharmacological modulation.
Topically administered capsaicin produces thermal allodynia, and this effect has been used to investigate pain transduction and its pharmacological modulation. This study investigated the parameters of topical capsaicin-induced thermal allodynia in unanesthetized rhesus monkeys and its pharmacological modulation by centrally acting compounds [a kappa-opioid agonist: (5alpha,7alpha,8beta)-(+)-N-methyl-N-(7-[1-pyrrolidinyl]-1-oxaspiro [4.5]dec-8-yl)-benzeneacetamide (U69,593); and noncompetitive N-methyl-d-aspartate (NMDA) antagonists: ketamine and MK-801 (dizocilpine)]. Rhesus monkeys (n = 4) were studied within the warm water tail withdrawal assay (20-s maximum latency), using thermal stimuli that are normally not noxious (38 and 42 degrees C). Capsaicin was applied topically on the tail (0.0013 and 0.004 M capsaicin solution on a 1-cm2 patch; 15-min contact). Topical capsaicin produced concentration-dependent thermal allodynia in both temperatures, robustly detected 15 to 90 min after topical capsaicin removal. A similar allodynic profile was observed with topical administration of the "endovanilloid" N-arachidonoyl-dopamine. The kappa-agonist U69,593 (0.01-0.1 mg/kg, s.c.) dose dependently prevented capsaicin (0.004 M)-induced allodynia in 38 and 42 degrees C, and the largest U69,593 dose also reversed ongoing allodynia within this model. Two NMDA antagonists, ketamine and MK-801 (0.32-1.8 and 0.032-0.056 mg/kg, respectively), also prevented capsaicin-induced allodynia in 38 degrees C, but only variably in 42 degrees C, at doses that did not cause robust thermal antinociceptive effects. At the largest doses studied, ketamine but not MK-801 also briefly reversed ongoing capsaicin-induced allodynia. The present model of topical capsaicin administration may be used to study antiallodynic effects of opioid and nonopioid compounds, as well as their ability to prevent and reverse allodynia, in unanesthetized nonhuman primates in the absence of tissue disruption.
Butelman
Eduardo R
ER
Rockefeller University, New York, NY 10021, USA. butelme@mail.rockefeller.edu
Ball
Jonathan W
JW
Harris
Todd J
TJ
Kreek
Mary Jeanne
MJ
D000613:Aminobutyrates / Q000627:therapeutic use; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D044482:Benzeneacetamides; D002211:Capsaicin; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000627:therapeutic use; D004399:Dynorphins / Q000627:therapeutic use; D005260:Female; D007649:Ketamine / Q000627:therapeutic use; D008253:Macaca mulatta; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control; D010147:Pain Measurement; D010446:Peptide Fragments / Q000627:therapeutic use; D011759:Pyrrolidines / Q000627:therapeutic use
D000613:Aminobutyrates; D000700:Analgesics; D044482:Benzeneacetamides; C401954:N(gamma)-acetyl-2,4-diaminobutyric acid; D010446:Peptide Fragments; D011759:Pyrrolidines; C061285:E 2078; D007649:Ketamine; D016291:Dizocilpine Maleate; D004399:Dynorphins; C045444:U 69593; D002211:Capsaicin