The long-lasting sensitization of primary afferent nociceptors induced by inflammation involves prostanoid and dopaminergic systems in mice

Abstract

In recent years, evidence that sensitization of primary afferent nociceptors is an important event associated with chronic pain has been accumulating. The present study aimed to evaluate the participation of the prostaglandin and sympathetic components in the long-lasting sensitization of nociceptors induced by acute inflammation in mice. The intraplantar administration of carrageenan (100 μg) enhanced the nociceptive response to a small dose of PGE2 (9 ng/paw) or dopamine (3 μg/paw) up to 30 days later. This long-lasting sensitization is dependent on dopaminergic and prostanoid systems, since the pre-treatment with chlorpromazine (3 μg/paw) or indomethacin (100 μg/paw), but not local (6 μg/paw) or systemic (6 mg/kg) treatment with morphine, prevented its development. In agreement with this idea, the previous intraplantar administration of hyperalgesic doses of PGE2 or dopamine also induced long-lasting sensitization, which was fully prevented by pretreatment with EP4 and D1 antagonists, respectively. In summary, the present work described in mice a long-lasting sensitization of nociceptors, initiated by an acute inflammatory stimulation and dependent on dopaminergic and prostanoid systems. The present data represent new insights on the mechanisms of peripheral sensitization that could contribute to establish the basis of new therapeutic strategies for acute and chronic inflammatory pain.