Pain
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Randomized Controlled Trial Multicenter Study
Endogenous opioid function mediates the association between laboratory-evoked pain sensitivity and morphine analgesic responses.
Predictors of responsiveness to opioid analgesic medications are not well understood. This study tested whether individual differences in endogenous opioid (EO) function are associated with analgesic responsiveness to morphine. In randomized, counterbalanced order over 3 sessions, 45 chronic low back pain participants and 31 healthy controls received an opioid antagonist (8 mg naloxone), morphine (0.08 mg/kg), or placebo. ⋯ These latter associations were significantly mediated by EO function for 4 of these 5 pain outcomes (all P values<0.05). In the laboratory-evoked pain context, opioid analgesic medications may supplement inadequate EO analgesia, with little incremental benefit in those with preexisting high EO function. Implications for personalized medicine are discussed.
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The biopsychosocial model is increasingly accepted in low back pain (LBP) research and clinical practice. In order to assess the role of psychological factors in the development and persistence of pain, a wide array of measures has been developed. Yet there is likely to be considerable conceptual overlap between such measures, and consequently, a lack of clarity about the importance of psychological factors. ⋯ Results confirmed that considerable overlap exists in psychological measures commonly used in LBP research. Most measures tap into patients' emotional distress. These findings help us to understand how psychological constructs relate together; implications for future research and clinical practice are discussed.
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In patients with complex regional pain syndrome (CRPS) type 1, processing of static tactile stimuli is impaired, whereas more complex sensory integration functions appear preserved. This study investigated higher order multisensory integration of body-relevant stimuli using the rubber hand illusion in CRPS patients. Subjective self-reports and skin conductance responses to watching the rubber hand being harmed were compared among CRPS patients (N=24), patients with upper limb pain of other origin (N=21, clinical control group), and healthy subjects (N=24). ⋯ However, patients with CRPS of the right hand reported significantly stronger neglect-like symptoms and significantly lower illusion strength of the affected hand than patients with CRPS of the left hand. The weaker illusion of CRPS patients with strong neglect-like symptoms on the affected hand supports the role of top-down processes modulating body ownership. Moreover, the intact ability to perceive illusory ownership confirms the notion that, despite impaired processing of proprioceptive or tactile input, higher order multisensory integration is unaffected in CRPS.
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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.