Leukocytes as mediators of pain and analgesia.

In inflammation, resident cells and infiltrating leukocytes produce proalgesic mediators. Although these mediators induce pain, the role of specific cell populations is still controversial. In addition, resident cells and leukocytes also generate analgesic mediators that counteract inflammatory pain, including anti-inflammatory cytokines, endocannabinoids, and opioid peptides. Chemokines and adhesion molecules orchestrate the migration of opioid peptide-containing leukocytes to inflamed tissue. Leukocytes secrete opioid peptides under stressful conditions or in response to releasing agents (eg, corticotropin-releasing factor and chemokines). Secretion requires intracellular calcium mobilization and activation of phosphinositol-3 kinase and p38 mitogen activated kinase. Following release, opioid peptides bind to receptors on peripheral sensory neurons and produce analgesia in animal models and humans. This review presents recent findings on the role of leukocytes in the generation and inhibition of inflammatory pain.