Pain-related disability and effects of chronic morphine in the adjuvant-induced arthritis model of chronic pain.
Functional disability has been identified as one of the most important aspects of chronic pain, yet modeling pain-related disability has received little attention. Adjuvant-induced arthritis was induced, and one group of arthritic rats was implanted with SC 75-mg morphine pellets 1 week postadjuvant, and reimplanted every 2 weeks thereafter. The results confirm that the rodent adjuvant-induced arthritis model of severe chronic pain can be used to model pain-related disability: spontaneous activity levels and ambulatory function were reduced in arthritic rats and they exhibited substantial weight loss. The results of the present study suggest that the operant delayed nonmatching-to-position task can be used as a measure of pain-related disability, which may be especially relevant to the effects of chronic pain on performance in a work setting. The delayed nonmatching-to-position operant bar-pressing task is an "apical" test that is sensitive to deficits across a wide range of behavioral functions: motor ability, attention, motivation, learning, and memory, and arthritic rats were severely impaired in this task. In addition, analgesic treatments that impair functional abilities in normal healthy rats may actually improve the performance of rats exhibiting pain-related disability. Previous work demonstrated that acute morphine injections of only 4 mg/kg impaired performance in the delayed matching-to-position task. The results of the present study demonstrate that chronic morphine attenuates the degree of pain-related disability exhibited by arthritic rats in the test of ambulatory function and the delayed nonmatching-to-position bar-pressing test. These results demonstrate that novel analgesic treatments can be screened preclinically, both with respect to their direct analgesic effects, and with respect to their ability to reduce pain-related disability.
Cain
C K
CK
CytoTherapeutics Inc., Providence, RI 02906, USA.
Francis
J M
JM
Plone
M A
MA
Emerich
D F
DF
Lindner
M D
MD
D000818:Animals; D001169:Arthritis, Experimental / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D004185:Disability Evaluation; D004193:Discrimination Learning / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D010147:Pain Measurement / Q000662:veterinary; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew
D009020:Morphine