Pain
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Chronic neuropathic pain is often a severe and inadequately treated consequence of spinal cord injury (SCI). Recent findings suggest that SCI pain is promoted by spontaneous activity (SA) generated chronically in cell bodies of primary nociceptors in dorsal root ganglia (DRG). Many nociceptors express transient receptor potential V1 (TRPV1) channels, and in a preceding study most dissociated DRG neurons exhibiting SA were excited by the TRPV1 activator, capsaicin. ⋯ TRPV1 knockdown also decreased the incidence of SA in dissociated nociceptors after SCI. Prolonged application of very low concentrations of capsaicin produced nondesensitizing firing similar to SA, and this effect was enhanced by prior SCI. These results show that TRPV1 makes important contributions to pain-related hypersensitivity long after SCI, and suggest a role for TRPV1-dependent enhancement of nociceptor SA that offers a promising target for treating chronic pain after SCI.
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This study aimed to investigate the modulating effects of emotional context on pain perception in 16 patients with fibromyalgia syndrome (FMS) and 16 healthy control (HC) subjects. An infrared laser was used to apply individually adapted painful stimuli to the dorsum of the left hand. The emotional background of the painful stimuli was modulated by concurrent presentations of negative, neutral, and positive picture stimuli selected from the International Affective Picture System. ⋯ In contrast, FMS patients showed a quadratic trend for pain intensity ratings indicating a lack of pain reduction by the positive pictures. In addition, the FMS patients showed less activation in secondary somatosensory cortex, insula, orbitofrontal cortex, and anterior cingulate cortex during the positive picture pain trials. Our results suggest that fibromyalgia patients are less efficient in modulating pain by positive affect and may benefit less from appetitive events than healthy control subjects.
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Randomized Controlled Trial
Hypnotic susceptibility modulates brain activity related to experimental placebo analgesia.
Identifying personality traits and neural signatures that predict placebo responsiveness is important, both on theoretical and practical grounds. In the present functional magnetic resonance imaging (fMRI) study, we performed multiple-regression interaction analysis to investigate whether hypnotic susceptibility (HS), a cognitive trait referring to the responsiveness to suggestions, explains interindividual differences in the neural mechanisms related to conditioned placebo analgesia in healthy volunteers. HS was not related to the overall strength of placebo analgesia. ⋯ During pain perception, activity in the regions reflecting attention/arousal (bilateral anterior thalamus/left caudate) and self-related processing (left precuneus and bilateral posterior temporal foci) was negatively related to the strength of the analgesic placebo response in subjects with higher HS, but not in subjects with lower HS. These findings highlight HS influences on brain circuits related to the placebo analgesic effects. More generally, they demonstrate that different neural mechanisms can be involved in placebo responsiveness, depending on individual cognitive traits.
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Neuropathic pain resulting from spinal hemisection or selective spinal nerve ligation is characterized by an increase in membrane-bound tumor necrosis factor-alpha (mTNFα) in spinal microglia without detectable release of soluble TNFα (sTNFα). In tissue culture, we showed that a full-length transmembrane cleavage-resistant TNFα (CRTNFα) construct can act through cell-cell contact to activate neighboring microglia. We undertook the current study to test the hypothesis that mTNFα expressed in microglia might also affect the phenotype of primary sensory afferents, by determining the effect of CRTNFα expressed from COS-7 cells on gene expression in primary dorsal root ganglia (DRG) neurons. ⋯ Exposure to sTNFα produced an increase only in CCL2 expression and release. Treatment of the cells with an siRNA against tumor necrosis factor receptor 2 (TNFR2) significantly reduced CRTNFα-induced gene expression changes in DRG neurons, whereas administration of CCR2 inhibitor had no significant effect on CRTNFα-induced increase in gene expression and CCL2 release in DRG neurons. Taken together, the results of this study suggest that mTNFα expressed in spinal microglia can facilitate pain signaling by up-regulating the expression of cation channels and CCL2 in DRG neurons in a TNFR2-dependent manner.