Pain
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Rheumatoid arthritis (RA) is a chronic autoimmune arthritis that affects approximately 1% of the population. Synovial inflammation cannot fully explain the level of pain reported by patients and facilitation of pain processing at the spinal level has been implicated. We characterized the K/BxN serum transfer arthritis model as a model of joint inflammation-induced pain and examined pharmacologic responsiveness and spinal glia activation. ⋯ ATF3, a marker of nerve injury, was significantly increased in the lumbar dorsal root ganglia during the late phase (day 28). Hence, serum transfer in the K/BxN serum transfer arthritis model produces a persistent pain state, where the allodynia during the inflammatory state is attenuated by TNF and prostaglandin inhibitors, and the pharmacology and histochemistry data suggest a transition from an inflammatory state to a state that resembles a neuropathic condition over time. Therefore, the K/BxN serum transfer model represents a multifaceted model for studies exploring pain mechanisms in conditions of joint inflammation and may serve as a platform for exploring novel treatment strategies for pain in human arthritic conditions.
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Brief noxious heat evokes more intense pain in women than in men; however, sex differences in the intensity of pain sensations evoked in hairy and glabrous skins are not clearly understood. Glabrous skin putatively lacks the type of A-delta nociceptors that underlie heat-evoked sharp sensation. Therefore, we assessed whether noxious heat-evoked pain qualities differed for hairy and glabrous skins and whether sex differences exist in these evoked pains. ⋯ Sharp, stinging and cutting sensations were evoked in glabrous skin, but the magnitude of these sensations was greater in hairy skin than glabrous skin; an effect only in females. Also, there was no sex difference in sharp sensation and annoyance in glabrous skin. These findings suggest that sharp sensations are evoked more prominently in hairy than in glabrous skin of women and that sharp sensations and annoyance play a prominent role in mediating aspects of pain-evoked from hairy skin in women.
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The primary purpose of the present study was to examine the temporal stability of communicative and protective pain behaviors in patients with chronic back pain. The study also examined whether the stability of pain behaviors could be accounted for by patients' levels of pain severity, catastrophizing, or fear of movement. Patients (n=70) were filmed on two separate occasions (i.e., baseline, follow-up) while performing a standardized lifting task designed to elicit pain behaviors. ⋯ Regression analyses also showed that pain behaviors remained stable when accounting for patients' levels of catastrophizing and fear of movement. Discussion addresses the potential contribution of central neural mechanisms and social environmental reinforcement contingencies to the stability of pain behaviors. The discussion also addresses how treatment interventions specifically aimed at targeting pain behaviors might help to augment the overall impact of pain and disability management programs.
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A novel cell-cell signaling by microglial transmembrane TNFα with implications for neuropathic pain.
Neuropathic pain is accompanied by neuroimmune activation in dorsal horn of spinal cord. We have observed that in animal models this activation is characterized by an increased expression of transmembrane tumor necrosis factor α (mTNFα) without the release of soluble tumor necrosis factor α (sTNFα). Herein we report that the pain-related neurotransmitter peptide substance P (SP) increases the expression of mTNFα without the release of sTNFα from primary microglial cells. ⋯ In order to evaluate the biological function of uncleaved mTNFα, we transfected COS-7 cells with a mutant full-length TNFα construct resistant to cleavage by TACE. Coculture of COS-7 cells expressing the mutant TNFα with microglial cells led to microglial cell activation indicated by increased OX42 immunoreactivity and release of macrophage chemoattractant peptide 1 (CCL2) by direct cell-cell contact. These results suggest a novel pathway through which the release of SP by primary afferents activates microglial expression of mTNFα, establishing a feed-forward loop that may contribute to the establishment of chronic pain.
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The ability of a painful stimulus to suppress pain in another, remote area (DNIC) has been intensely studied. However, the effect of the distance between the two painful stimuli and the attentional factors during the measurement of pain perception received minimal treatment. We evaluated the effect of these factors on DNIC and on the interaction between DNIC and spatial summation (SS) of pain. ⋯ However, the instruction to summate attenuated DNIC and the DNIC instruction attenuated SS of pain. Attention to the conditioning stimulus induced a stronger DNIC than attention to the test stimulus (p<0.001). We conclude that (1) DNIC and SS of pain appear to be antagonistic processes. (2) DNIC is affected by the distance between two noxious stimuli and to a lesser extent, by attention. (3) The interaction between DNIC, SS and attention is complex and reflects the role of sensory-cognitive integration in pain perception.