The journal of pain : official journal of the American Pain Society
-
Evidence of support for sensory changes during minor depression and sadness is scarce and the neural mechanisms are unclear. We assessed central pain processing engaged in nociceptive C-fiber polymodal activity by examining the perception of a non-noxious unpleasant burning sensation induced by a thermal grill illusion, in 26 nonpatients with minor depression (19 females) and 28 healthy subjects (18 females), between 19 and 61 years old and pain free at the study. Controls were also subjected to induction of transient moods. Subjects with depression reported increased pain perception; this increase was more pronounced for the affective dimension of pain (unpleasantness) than for its sensory dimension (intensity). The perception of pain unpleasantness, pain intensity, and overall pain showed positive and linear correlations with depression levels measured by Zung's and Beck's scales. In controls, sad mood induction only increased the scores assigned to negative mood-describing adjectives; the perception of pain intensity, unpleasantness, and overall pain were significantly increased following sad, but not neutral or elevated, mood inductions. Yet, pain intensity and unpleasantness were correlated linearly and reciprocally to positive, instead of negative, mood-describing adjective scores. Thus, there is a central thermal hyperalgesia in subjects with minor depression and sadness. ⋯ There is a central thermal hyperalgesia in subjects with minor depression, probably associated with an enhanced central processing of nociceptive C-fiber polymodal activity at anterior cingulate cortex, that is predominately expressed as an increased unpleasantness and that could be in part counteracted by behavioral therapies leading to mood elevation.
-
Cytokines, essential mediators of inflammatory and immune responses, play an important role in the pathophysiological processes associated with neuropathic pain following peripheral nerve injury. Recently, a novel proinflammatory cytokine, the interleukin (IL)-17, was found to orchestrate inflammatory responses in a wide range of inflammatory and autoimmune diseases of the nervous system. Here, we investigated the role of IL-17 in mediating neuroinflammation and pain hypersensitivity using the neuropathic pain model of partial ligation of the sciatic nerve in mice. Compared to wild-type, IL-17 knockout (KO) mice displayed significantly decreased mechanical pain hypersensitivity as well as decreased infiltration of T cells and macrophages to the injured sciatic nerves and the L3-L5 dorsal root ganglia and decreased activation of microglia and astrocytes in the L3-5 dorsal and ventral horns of the spinal cord. Further, intraplantar and intraneural injection of recombinant IL-17 into the hind paw and the sciatic nerve, respectively, induced both mechanical allodynia and thermal hyperalgesia, whereas intrathecal injection produced thermal hyperalgesia. IL-17 administration was associated with a significant increase in the numbers of infiltrating neutrophils and activated dendritic cells in the injected hind paws and infiltrating neutrophils in the injected sciatic nerves. Taken together, our results demonstrate that IL-17 contributes to the regulation of immune cell infiltration and glial activation after peripheral nerve injury and the ensuing neuropathic pain. ⋯ IL-17 is an important regulator of immune responses and is involved in inducing and mediating proinflammatory reactions. Using IL-17 KO mice, we have demonstrated that IL-17 contributes to neuroinflammatory responses and pain hypersensitivity following neuropathic injury. This work identifies IL-17 as a potential therapeutic target in neuropathic pain.