Efficacy of chronic morphine in a rat model of cancer-induced bone pain: behavior and in dorsal horn pathophysiology.
Morphine is one of the main analgesics in cancer-induced bone pain (CIBP). To investigate the efficacy of morphine in CIBP and alteration in dorsal horn pathophysiology, systemic morphine was administered (3 mg/kg) bi-daily between days 11 and 15 after MRMT-1 carcinoma cell injections (compared with a single injection (3 mg/kg) of morphine on day 15, and acute spinal morphine (0.1, 1, 10 microg/50 microL). The chronic systemic morphine schedule significantly attenuated pain behavior (von Frey 15 g; P < .01) to a greater extent than acute systemic morphine (von Frey 15 g; P < .05). In vivo electrophysiology (day 15 chronic systemic morphine) showed an attenuation of hyperexcitable wide dynamic range (WDR) neurons, but the abnormal raised WDR to nociceptive specific neuronal ratio remained. Acute spinal morphine attenuated electrical and natural WDR neuronal response in shams at a lower dose (1 microg) compared with cancer (10 microg). Chronic morphine is more effective at attenuating pain-related behaviors than single doses, although the dorsal horn retains a pathophysiologic characterization.


CONCLUSIONS
This study confirms the resemblance of the rat model to human CIBP with respect to the efficacy of morphine and further suggests that adjuvant therapy is required to reverse the dorsal horn pathophysiology.
Urch
Catherine E
CE
Department of Pharmacology, University College London, London, United Kingdom. c.urch@ucl.ac.uk
Donovan-Rodriguez
Tansy
T
Gordon-Williams
Richard
R
Bee
Lucy A
LA
Dickenson
Anthony H
AH
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000701:Analgesics, Opioid / Q000008:administration & dosage; D000771:Anesthesia, Intravenous; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001859:Bone Neoplasms / Q000150:complications* / Q000556:secondary; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007278:Injections, Spinal; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000150:complications / Q000556:secondary; D009020:Morphine / Q000008:administration & dosage*; D009619:Nociceptors / Q000187:drug effects* / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010148:Intractable Pain / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000637:transplantation
D000701:Analgesics, Opioid; D009020:Morphine