Central noradrenergic and cholinergic modulation of formaldehyde-induced pedal inflammation and nociception in rats.

Possible central noradrenergic and cholinergic modulation of acute peripheral inflammation was investigated in rats, adopting the formaldehyde-induced pedal inflammation as the experimental model. Intracerebroventricularly (icv) administered noradrenaline (NA), alpha-adrenoceptor agonist, L-phenylephrine, alpha-2 adrenoceptor agonist, clonidine and non-selective beta-adrenoceptor blocker, propranolol, suppressed formaldehyde-induced inflammation producing a decrease in oedema volume and increase in pain threshold. Conversely, both noradrenergic neuron degenerator, 6-hydroxydopamine (6-OHDA) and non-selective alpha-adrenoceptor antagonist, phenoxybenzamine produced an increase in paw oedema along with an augmentation of pain. Significant oedema augmenting effects were also produced by central excitatory neurotransmitter, acetylcholine (ACh) on icv administration. ACh also produced pro-nociceptive action. An ACh antagonist, scopolamine and ACh synthesis inhibitor, hemicholinium-3 (HC) reduced pedal oedema and produced analgesia. The results of this study indicate that central NA exerts an inhibitory effect on peripheral oedema and pain whereas, ACh has an augmenting effect on formaldehyde-induced peripheral inflammation.