Pain behavior measures to quantitate joint pain and response to neurotoxin treatment in murine models of arthritis.
OBJECTIVE
To evaluate the validity of newly developed pain behavior measures in two murine models of inflammatory arthritis and to determine the ability of these measures to evaluate the analgesic effectiveness of intra-articular (IA) botulinum toxin type A (BoNT/A) for treatment of arthritis pain.


METHODS
Acute inflammatory arthritis was produced in adult female mice by IA injection of carrageenan and chronic inflammatory arthritis by IA injection of CFA. The presence of arthritis was confirmed by the presence of swelling and erythema. A menu of pain behavior measures was devised for quantitating pain in these models including tenderness, and spontaneous nocturnal wheel running. Toxicity due to neurotoxin was measured as gross limb weakness and impaired functional ability during wheel running.


RESULTS
Tenderness measures and spontaneous nocturnal wheel-running are valid measures of arthritis pain and are sensitive to the effects of analgesia. Narcotic analgesics are effective, but in fully analgesic doses impair wheel-running. IA BoNT/A is an effective analgesic for chronic arthritis pain, but not for acute arthritis pain. High doses can produce local limb muscle weakness, which impairs wheel-running function. Doses of botulinum toxin that are not toxic retain their analgesic function.


CONCLUSIONS
Tenderness and spontaneous pain behavior measures are valid and sensitive for the measurement of pain and analgesia in murine models of inflammatory arthritis. Effective narcotic analgesia produces a decline in function in mice similar to that seen in humans. IA neurotoxin is a promising therapy for chronic inflammatory arthritis but may not be effective for acute arthritis pain.
Krug
Hollis E
HE
VA Medical Center, Minneapolis, MN 55417, USA. krugx002@umn.edu
Frizelle
Sandra
S
McGarraugh
Pari
P
Mahowald
Maren L
ML
D000818:Animals; D018771:Arthralgia / Q000175:diagnosis* / Q000188:drug therapy* / Q000209:etiology; D001168:Arthritis / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009498:Neurotoxins / Q000008:administration & dosage; D010147:Pain Measurement / Q000187:drug effects*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D009498:Neurotoxins; D019274:Botulinum Toxins, Type A