Pain
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The aim of this study was to examine the joint role of demographic, clinical, and psychological variables as predictors of acute postsurgical pain in women undergoing hysterectomy due to benign disorders. A consecutive sample of 203 women was assessed 24 hours before (T1) and 48 hours after (T2) surgery. Baseline pain and predictors were assessed at T1 and postsurgical pain and analgesic consumption at T2. ⋯ Findings revealed an integrative heuristic model that accounts for the joint influence of demographic, clinical, and psychological factors on postsurgical pain intensity and severity. In further mediation analysis, pain catastrophizing emerged as a full mediator between presurgical anxiety and postsurgical pain intensity. The potential clinical implications for understanding, evaluating, and intervening in postsurgical pain are discussed.
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Cholecystokinin (CCK) has been suggested to be both pro-nociceptive and "anti-opioid" by actions on pain-modulatory cells within the rostral ventromedial medulla (RVM). One consequence of activation of RVM CCK₂ receptors may be enhanced spinal nociceptive transmission; but how this might occur, especially in states of pathological pain, is unknown. Here, in vivo microdialysis was used to demonstrate that levels of RVM CCK increased by approximately 2-fold after ligation of L₅/L₆ spinal nerves (SNL). ⋯ Spinal administration of naproxen, a nonselective COX-inhibitor, significantly attenuated RVM CCK-induced hindpaw tactile hypersensitivity. RVM-CCK also resulted in a 2-fold increase in spinal 5-hydroxyindoleacetic acid (5-HIAA), a 5-hydoxytryptophan (5-HT) metabolite, as compared with controls, and mechanical hypersensitivity that was attenuated by spinal application of ondansetron, a 5-HT₃ antagonist. The present studies suggest that chronic nerve injury can result in activation of descending facilitatory mechanisms that may promote hyperalgesia via ultimate release of PGE₂ and 5-HT in the spinal cord.
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Critically ill pediatric patients frequently receive prolonged analgesia and sedation to provide pain relief and facilitate intensive care therapies. Iatrogenic withdrawal syndrome occurs when these drugs are stopped abruptly or weaned too rapidly. We investigated the validity and generalizability of the Withdrawal Assessment Tool-1 (WAT-1) in children during weaning of analgesics and sedatives. ⋯ Factor analyses confirmed that motor-related symptoms and behavioral state accounted for the most variance in WAT-1 scores. Supporting construct validity, cumulative opioid exposures were greater [40.2 (19.7-83.4) vs 17.6 (14.6-39.7) mg/kg, P=.004], length of opioid treatment before weaning was longer [7 (6-11) vs 5 (5-8)days, P=.004], and length of weaning from opioids was longer [10 (6-14) vs 6 (3-9)days, P=.008] in subjects with WAT-1 scores of ≥ 3 compared to subjects with WAT-1 scores of <3. The WAT-1 shows good psychometric performance and generalizability when used to assess clinically important withdrawal symptoms in pediatric intensive care and general ward settings.
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Osteoarthritis is a degenerative joint disease with pain and loss of joint function as major pathological features. Recent studies show that proteasome inhibitors reduce pain in various pathological conditions. We evaluated the effects of MG132, a reversible proteasome inhibitor on pain and joint destruction in a rat model of osteoarthritis. ⋯ Furthermore, the upregulated expression of MMP-3, SP, and CGRP in the arthritic rats was normalized by MG132 administration. We conclude that the proteasome inhibitor MG132 reduces pain and joint destruction, probably by involving the peripheral nervous system, and that changes in SP and CGRP expression correlate with alterations in behavioural responses. Our findings suggest that nontoxic proteasome inhibitors may represent a novel pharmacotherapy for osteoarthritis.
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Chemokine signaling is important in neuropathic pain, with microglial cells expressing CCR2 playing a well-established key role. DAPTA, a HIV gp120-derived CCR5 entry inhibitor, has been shown to inhibit CCR5-mediated monocyte migration and to attenuate neuroinflammation. We report here that as a stabilized analog of DAPTA, the short peptide RAP-103 exhibits potent antagonism for both CCR2 (half maximal inhibitory concentration [IC50] 4.2 pM) and CCR5 (IC50 0.18 pM) in monocyte chemotaxis. ⋯ RAP-103 relieves behavioral hypersensitivity, probably through either or both CCR2 and CCR5 blockade, because by using genetically deficient animals, we demonstrated that in addition to CCR2, CCR5 is also required for the development of neuropathic pain. Moreover, RAP-103 is able to reduce spinal microglial activation and monocyte infiltration, and to inhibit inflammatory responses evoked by peripheral nerve injury that cause chronic pain. Our findings suggest that targeting CCR2/CCR5 should provide greater efficacy than targeting CCR2 or CCR5 alone, and that dual CCR2/CCR5 antagonist RAP-103 has the potential for broad clinical use in neuropathic pain treatment.