Pretreatment with gangliosides reduces abnormal nociceptive responses associated with a rodent peripheral mononeuropathy.
A peripheral mononeuropathy was produced in adult male rats by placing loosely constrictive ligatures around the common sciatic nerve. As reported by others, this procedure reliably results in postoperative behavior indicative of hyperalgesia, allodynia, and potentially, spontaneous pain. In these experiments, thermal hyperalgesia was assessed by measuring foot-withdrawal latencies to radiant heat aimed at the plantar surface of rat hind paws. Behaviors potentially indicative of spontaneous pain were assessed by rating spontaneous hind paw guarding positions. Rats with sciatic nerve ligation were divided into 5 groups (n = 6/group). Three groups received injections (i.p.) of either 10, 20 or 40 mg/kg of cerebral ganglioside mixture, GA. The 4th group was injected with 10 mg/kg of the purified ganglioside GM1, and the 5th group received an equal volume of saline. All injections were given daily for 2 days before surgery, the day of surgery and 9 days after surgery. All animals were behaviorally assessed for 2 days prior to surgery, the day of surgery, as well as 1, 3, 5, 7, and 10 days afterwards. All 5 groups had significantly reduced latencies to hind paw withdrawal on the side ipsilateral to sciatic nerve ligation. However, these hyperalgesic responses were significantly attenuated in rats receiving GA or GM1 pretreatment. These data suggest that this animal model of peripheral neuropathic pain is sensitive to pharmacological manipulations useful for understanding mechanisms of neuropathic pain, including mechanisms related to excitotoxic processes. Such studies could lead to development of clinical approaches to treat this disorder.
Hayes
Ronald L
RL
Medical College of Virginia, MCV Station, Richmond, VA 23298 USA Department of Neurosurgery, University of Messina, MessinaItaly Fidia Pharmaceuticals, PadovaItaly.
Mao
Jianren
J
Price
Donald D
DD
Germano
Antonino
A
d'Avella
Dominico
D
Fiori
Mario
M
Mayer
D J
DJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005732:Gangliosides / Q000627:therapeutic use*; D006358:Hot Temperature; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains
D005732:Gangliosides