• Louise Henriette Pedersen, Jørgen Scheel-Krüger, and Gordon Blackburn-Munro.
• Department of Pharmacology, NeuroSearch A/S, 93 Pederstrupvej, DK-2750 Ballerup, Denmark.
• Pain. 2007 Jan 1; 127 (1-2): 17-26.

AbstractThe contribution of the amygdala to neuropathic pain processing in animals has not been clearly acknowledged. To assess the relative contribution of amygdala GABA-A receptors in mediating sensory-discriminative and affective-motivational pain components, the GABA-A receptor agonist muscimol and the antagonist bicuculline (both 10-25 ng/microl) were administered by acute bilateral injection directly into the central amygdala in rats with a chronic constriction injury (CCI). Escape/avoidance behaviour reflecting the affective-motivational dimension of pain was measured using a light/dark chamber in combination with suprathreshold nociceptive stimulation, and was defined as a shift from the 'non-aversive' dark area of the chamber to the 'aversive' light area. Hindpaw mechanical allodynia and mechanical hyperalgesia thresholds reflecting the sensory-discriminative dimension of pain were determined prior to and following escape/avoidance testing. Muscimol administration into the amygdala attenuated escape/avoidance behaviour and reversed hindpaw mechanical hypersensitivity in CCI rats; the magnitude of reduction in escape/avoidance behaviour was 2- to 3-fold greater than mechanical allodynia. Surprisingly, administration of bicuculline also attenuated escape/avoidance behaviour but had no effect on nociceptive behaviours. The muscimol-induced reversal of hindpaw mechanical hypersensitivity was completely blocked by co-administration of bicuculline, in contrast to escape/avoidance behaviour. Motility behaviour was unaffected by injection of either drug as determined in the open field test. Thus, amygdala GABA-A receptors appear to play an important role in sensory and especially affective pain processing in neuropathic rats. Furthermore, after nerve injury reflex nociceptive behaviours appear to be under tonic control by descending inputs, which originate from or are modulated within the amygdala.

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