Pathophysiology of acute inflammatory pain: integration between inflammation and nociception

Abstract

Acute inflammatory pain represents an important clinical and public health challenge, being the main complaint in emergency services. It begins with tissue injury, which activates innate immune receptors and leads to the release of cytokines, prostaglandins, and algiogenic mediators, promoting vasodilation, edema, and sensitization of peripheral nociceptors. Among the main inflammatory mediators are PGE2, NGF, IL-1β, TNF-α, as well as the chemokines CCL2 and CX3CL1 (fractalkine). This inflammatory environment decreases the activation threshold of nociceptors, intensifying the pain response. Transduction occurs through the activation of TRPV1 and Nav1.7/1.8 channels, resulting in action potentials that are transmitted by Aδ and C fibers to the dorsal horn of the spinal cord. There, synapses with second-order neurons trigger the ascending transmission of pain through the spinothalamic, spinomesencephalic, and spinoreticular tracts, reaching structures such as the thalamus, somatosensory, cingulate, and insular cortices, as well as limbic regions, shaping the sensory and emotional experience of pain. Modulation occurs both through local inhibitory interneurons and through descending pathways originating in the brainstem, using neurotransmitters such as GABA, serotonin, norepinephrine, and endogenous opioids. Microglial activation and central neuroinflammation may also perpetuate pain. An integrated understanding of the neurobiology of acute pain is essential to prevent its chronification and to propose effective therapeutic approaches.