Pain
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Neuroimaging studies of patients with chronic pain have shown that neurotransmitter abnormalities, including increases in glutamate and decreases in GABA, could be responsible for the cortical hyperactivity and hyperalgesia/allodynia observed in some pain conditions. These finding are particularly evident in the insula, a brain region known to play a role in both the sensory-discriminative and the affective-motivational aspects of pain processing. However, clinical studies are not entirely able to determine the directionality of these findings, nor whether they are causal or epiphenomenon. ⋯ Increasing endogenous levels of GABA or enhancing signaling at inhibitory glycinergic receptors had similar effects as the glutamate receptor antagonists. In naive rats, increasing endogenous levels of glutamate, decreasing endogenous levels of GABA, or blocking strychnine-sensitive glycine receptors in the insula significantly increased thermal hyperalgesia and mechanical allodynia. These data support the hypothesis that an altered balance of excitatory and inhibitory neurotransmitters in brain regions such as the insula occurs in chronic pain states and leads to augmented central pain processing and increased pain sensitivity.
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Multicenter Study
Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study.
Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. ⋯ Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of -374 g (-479 to -269 g) for TP and -498 g (-609 to -386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future.