Pharmacological characterisation of place escape/avoidance behaviour in the rat chronic constriction injury model of neuropathic pain.
BACKGROUND
Classical pain tests performed in animals routinely measure evoked nociceptive behaviours. These almost exclusively reflect sensory processing of nociceptive transmission, although a recently described place escape/avoidance paradigm may be used to selectively assess affective pain processing.


OBJECTIVE
To establish if drugs with proven analgesic efficacy selectively attenuate sensory-discriminative or affective-motivational aspects of nociceptive processing.


METHODS
The mu-opioid receptor agonist morphine, the anti-epileptic gabapentin, the anti-depressant duloxetine, the 5HT1A receptor agonist 8-OH-DPAT, the GABA(A) receptor agonist gaboxadol and the mixed cannabinoid receptor agonist WIN55,212-2 were tested after systemic administration in the chronic constriction injury (CCI) model of neuropathic pain. For the place escape/avoidance paradigm, CCI rats had free access between the 'non-aversive' dark and 'aversive' light side of an enclosed chamber. Either the injured or non-injured hindpaw was routinely stimulated if the rat was in the dark or light area, respectively. Escape/avoidance behaviour was defined as a shift from the dark to the light area. Mechanical allodynia and hyperalgesia were determined prior to and following escape/avoidance testing.


RESULTS
Morphine (3 and 6 mg/kg), gabapentin (50 and 100 mg/kg), duloxetine (10 and 30 mg/kg) and 8-OH-DPAT (0.1 and 0.5 mg/kg) attenuated the time spent by CCI rats in the light area; gaboxadol (1 and 3 mg/kg) and WIN55,212-2 (0.3 and 1 mg/kg) were ineffective. Only gabapentin and 8-OH-DPAT attenuated mechanical nociceptive behaviours at non-sedative doses.


CONCLUSIONS
The place escape/avoidance paradigm may enable discrimination between selected drug classes on distinct components of sensory and affective pain processing in rats with neuropathic pain.
Department of Pharmacology, NeuroSearch A/S, 93 Pederstrupvej, 2750 Ballerup, Denmark. lhp@neurosearch.dk
Louise H
LH
Pedersen
Gordon
G
Blackburn-Munro
D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects*; D002908:Chronic Disease; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects*; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D009437:Neuralgia / Q000503:physiopathology*; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000700:Analgesics; D000701:Analgesics, Opioid; D000927:Anticonvulsants; D000928:Antidepressive Agents; D018755:GABA Agonists; D017366:Serotonin Receptor Agonists