Amygdala GABA-A receptor involvement in mediating sensory-discriminative and affective-motivational pain responses in a rat model of peripheral nerve injury

Abstract

The 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.

The effect of pain on cognitive function: A review of clinical and preclinical research

“…Decreased neurotransmission in the amygdala, by administration of the Gamma-aminobutyric acid (GABA)A receptor agonist muscimol or lesion of the central nucleus, has been shown to attenuate pain-induced avoidance behaviour i.e. impaired affective processing of pain (Pedersen et al, 2007).…”

Enhanced c‐Fos expression in the central amygdala correlates with increased thigmotaxis in rats with peripheral nerve injury

“…cognitive response to potential but absent threat) in response to aversive stimuli (LeDoux, 1998). Such lesions also attenuate escape‐avoidance behaviour associated with the chronic constriction model (CCI) (Pedersen et al., 2007). Clinical imaging studies have associated evoked pain with regional increases in perfusion in brain areas involved in affective‐motivational control, including the amygdala (Geha et al., 2007).…”

Hemispheric Lateralization of Pain Processing by Amygdala Neurons

“…The amygdala plays a critical role in the emotional response to pain and in pain modulation (Carrasquillo and Gereau 2007;Fields 2004;Gauriau and Bernard 2004;Heinricher and McGaraughty 1999;Ikeda et al 2007;Neugebauer et al 2004Neugebauer et al , 2006Pedersen et al 2007;Rhudy and Meagher 2001). Our previous studies focused on the right amygdala and showed central sensitization and synaptic plasticity in neurons of the latero-capsular division of the central nucleus (CeLC) in an animal model of arthritis pain (Bird et al 2005;Han et al 2005b;Neugebauer and Li 2003;Neugebauer et al 2003).…”