A rat model of unilateral hindpaw burn injury: slowly developing rightwards shift of the morphine dose-response curve.
Management of pain after burn injury is an unresolved clinical issue. In a rat model of hindpaw burn injury, we examined the effects of systemic morphine on nociceptive behaviors following injury. Injury was induced by immersing the dorsal part of one hindpaw into a hot water bath (85 degrees C) for 4, 7, or 12 s under pentobarbital anesthesia. Mechanical allodynia to von Frey filament stimulation and thermal hyperalgesia to radiant heat were assessed. Burn injury induced by the 12-s (but not 4-, or 7-s) hot water immersion resulted in reliable and lasting mechanical allodynia and thermal hyperalgesia evident by day 1. In addition, there was an upregulation of protein kinase Cgamma and a progressive downregulation of mu-opioid receptors within the spinal cord dorsal horn ipsilateral to injury as revealed by immunohistochemistry and Western blot. In both injured and sham rats, the anti-nociceptive effects of subcutaneous morphine were examined on post-injury days 7 and 14. While the morphine AD50 dose was comparable on day 7 between burn (1.61 mg/kg) and control (1.7 mg/kg) rats, the morphine dose-response curve was shifted to the right in burn-injured rats (4.6 mg/kg) on post-injury day 14 as compared with both the injured rats on post-injury day 7 and sham rats on day 14 (1.72 mg/kg). These data indicate that hindpaw burn injury reliably produces persistent mechanical allodynia and thermal hyperalgesia and that the reduced efficacy of morphine anti-nociception in chronic burn injury may be in part due to a downregulation of spinal mu-opioid receptors.
Wang
Shuxing
S
Pain Research Group, MGH Pain Center, WACC 324, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street, Boston, MA 02114, USA.
Lim
Grewo
G
Yang
Liling
L
Zeng
Qing
Q
Sung
Backil
B
Jeevendra Martyn
J A
JA
Mao
Jianren
J
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002056:Burns / Q000150:complications* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality / Q000502:physiology*; D006614:Hindlimb / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009020:Morphine / Q000627:therapeutic use*; D009294:Narcotics / Q000627:therapeutic use*; D010147:Pain Measurement / Q000379:methods; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D000199:Actins; D009294:Narcotics; D017450:Receptors, Opioid, mu; D009020:Morphine; C087857:protein kinase C gamma; D011493:Protein Kinase C