Antihyperalgesic effect of systemic dexmedetomidine and gabapentin in a rat model of monoarthritis.
The present study investigated the effects of systemic administration of dexmedetomidine, a selective alpha2 adrenergic receptor (alpha2AR) agonist, and gabapentin either alone or in combination on thermal hyperalgesia evoked by ankle joint inflammation. Monoarthritis of rat ankle joint was induced by an intra-articular injection of Complete Freund's Adjuvant (CFA). The paw withdrawal latency (PWL) from a thermal stimulus was measured in awake rats. Intraperitoneal (i.p.) injection of dexmedetomidine (2.5, 5, 10 and 20 microg/kg) or gabapentin (25, 50, 100 and 200 mg/kg) significantly and dose-dependently increased the PWL of the hindpaw ipsilateral to CFA-injected joint. The PWLs of the non-injected and normal saline (NS)-injected hindpaws were not significantly affected by the two agents at the most doses tested except the highest dose of dexmedetomidine (20 microg/kg). Although low dose of dexmedetomidine (2.5 microg/kg) or gabapentin (25 mg/kg) alone did not affect or lightly increased PWLs of the hindpaw ipsilateral to CFA-injected joint, a combination of dexmedetomidine and gabapentin (2.5 microg/kg+25 mg/kg, or 5 microg/kg+50 mg/kg) significantly reversed CFA-induced thermal hyperalgesia for 60 min without sedation/motor impairment. These results provide the first identification that co-application of dexmedetomidine and gabapentin may synergistically antagonize inflammatory pain, and this might prove to be beneficial in the treatment of arthritic pain.
Zhang
Wei-Shi
WS
Department of Anesthesiology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
Xu
Hua
H
Xu
Bo
B
Sun
Shan
S
Deng
Xiao-Ming
XM
Zhang
Yu-Qiu
YQ
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000588:Amines / Q000008:administration & dosage* / Q000627:therapeutic use; D000700:Analgesics / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D000843:Ankle Joint / Q000187:drug effects / Q000276:immunology*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage* / Q000627:therapeutic use; D020927:Dexmedetomidine / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005620:Freund's Adjuvant / Q000494:pharmacology; D000077206:Gabapentin; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D007270:Injections, Intra-Articular; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage* / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D020927:Dexmedetomidine; D000077206:Gabapentin; D005620:Freund's Adjuvant