The role of dorsal root reflexes in neurogenic inflammation

K.A Sluka; W.D Willis; K.N Westlund

doi:10.1016/S1082-3174(11)80045-0

In light of findings of a series of studies with an acute inflammatory model, it is proposed here that central events in the spinal cord dorsal horn are sufficient and necessary for initiation of neurogenic inflammation and the resultant persistent pain and hyperalgesia. It is hypothesized that the central control of peripheral inflammation and transmission of nociception occur through at least two separate multisynaptic pathways. Inflammation is initiated when afferent fibers release excitatory amino acids that act on non-NMDA glutamate receptors in the superficial dorsal horn, affecting both excitatory and inhibitory interneuronal circuits. Excitatory interneurons activate projection neurons through NMDA receptors to transmit signals leading to the perception of pain by higher brain centers. The increasing levels of excitatory amino acids would also increase the excitability of superficial dorsal horn interneuronal circuits, including GABAergic inhibitory interneurons, which would exert a presynaptic influence through GABA-A receptors on primary afferent endings. If the activation is powerful enough, a pathological response, known as dorsal root reflexes, occurs, in which action potentials begin firing antidromically back down the primary afferent fibers to the periphery. In this manner the inflammatory mediating peptides found in the afferents are released into the periphery, resulting in increasing inflammation and further afferent activation directed centrally. Through the central interneuronal circuits, other afferent fibers are recruited. Activation of these previously “silent” nociceptors and dorsal root reflexes results in the “vicious cycle” of pain and inflammation. All of these amplification events not only further increase the inflammation but result in a persistent pain state and hyperalgesia. Though these events are reversible in the case of the acute inflammatory model, dorsal root reflexes as an initiator of persistent pain should be considered for chronic pain models where other more complex factors come into play, including secondary intracellular events and the sympathetic nervous system.

The role of dorsal root reflexes in neurogenic inflammation

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