Pain
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This study examined the role of pain catastrophizing, fear of movement and depression as determinants of repetition-induced summation of activity-related pain. The sample consisted of 90 (44 women and 46 men) work-disabled individuals with chronic low back pain. Participants were asked to lift a series of 18 canisters that varied according to weight (2.9kg, 3.4kg, 3.9kg) and distance from the body. ⋯ Fear of movement, but not pain catastrophizing or depression, was associated with greater repetition-induced summation of pain. The findings point to possible neurophysiological mechanisms that could help explain why fear of pain is a robust predictor of pain-related disability. Mechanisms of repetition-induced summation of activity-related pain are discussed.
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Activation of P2X3,2/3 receptors by endogenous ATP contributes to the development of inflammatory hyperalgesia. Given the clinical importance of mechanical hyperalgesia in inflammatory states, we hypothesized that the activation of P2X3,2/3 receptors by endogenous ATP contributes to carrageenan-induced mechanical hyperalgesia and that this contribution is mediated by an indirect and/or a direct sensitization of the primary afferent nociceptors. Co-administration of the selective P2X3,2/3 receptors antagonist A-317491, or the non-selective P2X3 receptor antagonist, TNP-ATP, with carrageenan blocked the mechanical hyperalgesia induced by carrageenan, and significantly reduced the increased concentration of tumor necrosis factor alpha (TNF-alpha) and chemokine-induced chemoattractant-1 (CINC-1) but not of interleukin-1 beta (IL-1 beta) induced by carrageenan. ⋯ Intrathecal administration of oligonucleotides antisense against P2X3 receptors for seven days significantly reduced the expression of P2X3 receptors in the saphenous nerve and significantly reduced the mechanical hyperalgesia induced by carrageenan. We concluded that the activation of P2X3,2/3 receptors by endogenous ATP is essential to the development of the mechanical hyperalgesia induced by carrageenan. Furthermore, we showed that this essential role of P2X3,2/3 receptors in the development of carrageenan-induced mechanical hyperalgesia is mediated by an indirect sensitization of the primary afferent nociceptors dependent on the previous release of TNF-alpha and by a direct sensitization of the primary afferent nociceptors.
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The ultra-short-acting mu-opioid receptor (MOR) agonist remifentanil enhances postsurgical pain when used as main anesthetic in animal models and man. Although the mechanism/s involved are poorly characterized, changes in opioid receptor expression could be a relevant feature. Using a mouse model of postoperative pain, we assessed the expression of MOR and delta opioid receptors (DORs) and the efficacy of Herpes Simplex vector-mediated proenkephalin release (SHPE) preventing postoperative nociceptive sensitization induced by remifentanil or surgical incision. ⋯ Pre-treatment with SHPE 7 days before manipulation prevented remifentanil-induced thermal hyperalgesia and mechanical allodynia and the increase in incisional pain observed when surgery was performed under remifentanil anesthesia. SHPE also prevented surgically induced allodynia but not hyperalgesia, which was blocked by the additional administration of RB101, an enkephalinase inhibitor. The study suggests that down-regulation of DOR contributes to remifentanil and surgery-induced nociception, and that postoperative pain is completely reversed by increasing enkephalin levels in the spinal cord and the periphery.
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Inflammatory diseases associated with pain are often difficult to treat in the clinic due to insufficient understanding of the nociceptive pathways involved. Recently, there has been considerable interest in the role of reactive oxygen species (ROS) in inflammatory disease, but little is known of the role of hydrogen peroxide (H(2)O(2)) in hyperalgesia. In the present study, intraplantar injection of H(2)O(2)-induced a significant dose- and time-dependent mechanical and thermal hyperalgesia in the mouse hind paw, with increased c-fos activity observed in the dorsal horn of the spinal cord. ⋯ Thermal, but not mechanical, hyperalgesia in response to H(2)O(2) (i.pl.) was longer lasting in TRPV1 wild type mice compared to TRPV1 knockouts. It is unlikely that downstream lipid peroxidation was increased by H(2)O(2). In conclusion, we demonstrate a notable effect of H(2)O(2) in mediating inflammatory hyperalgesia, thus highlighting H(2)O(2) removal as a novel therapeutic target for anti-hyperalgesic drugs in the clinic.
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Randomized Controlled Trial Controlled Clinical Trial
Subcutaneous Botulinum toxin type A reduces capsaicin-induced trigeminal pain and vasomotor reactions in human skin.
The present human study aimed at investigating the effect of subcutaneous administration of Botulinum toxin type A (BoNT/A) on capsaicin-induced trigeminal pain, neurogenic inflammation and experimentally induced cutaneous pain modalities. Fourteen healthy males (26.3+/-2.6 years) were included in this double-blind and placebo-controlled trial. The subjects received subcutaneous BoNT/A (22.5U) and isotonic saline in the mirror sides of their forehead. ⋯ BoNT/A reduced blood flow (F(1,26)=109.5, P<0.001) and skin temperature (F(1,26)=63.1, P<0.001) at the capsaicin injection sites compared to saline and its suppressive effect was maximal at days 3 and 7 (P<0.05, post hoc test). BoNT/A elevated cutaneous heat pain thresholds (F=17.1, P<0.001) compared to saline; however, no alteration was recorded for electrical or pressure pain thresholds (P>0.05). Findings from the present study suggest that BoNT/A appears to preferentially target Cfibers and probably TRPV1-receptors, block neurotransmitter release and subsequently reduce pain, neurogenic inflammation and cutaneous heat pain threshold.