Articles: hyperalgesia.
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Clinical observations indicate that cutaneous hyperalgesia may arise from pain located in deep structures. The objective of this study was to investigate whether combined sensitization of deep and superficial somatic tissues facilitates skin hyperalgesia. ⋯ Using skin and deep tissue pain sensitization models simultaneously, no significant synergistic effects were found within the 3-day investigation suggesting little integration between the two phenomena in this period.
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The transient receptor potential cation channel subfamily M 8 (TRPM8) agonist L-menthol has been used traditionally for its topical counterirritant properties. Although the use of topical L-menthol for pain is casuistically established, evidence regarding its efficacy is negligible. This study aimed to characterize the effect of L-menthol as a counterirritant on cutaneous pain and hyperalgesia provoked by topical application of the transient receptor potential cation channel, subfamily A, member 1 (TRPA1) agonist trans-cinnamaldehyde (CA). In a randomized, double-blinded study CA was applied to a 3 × 3-cm area of the volar forearm evoking neurogenic inflammation, pain, mechanical, and thermal hyperalgesia in 14 healthy volunteers. In different sessions, 10% CA alone or 40% L-menthol applied simultaneously with 10% CA were administered for 20 minutes, throughout which the subjects rated the pain intensity on a visual analogue scale of 0 to 10. Extensive quantitative sensory testing was conducted and superficial blood flow (neurogenic inflammation) was recorded. Administration of CA evoked spontaneous pain, neurogenic inflammation, thermal hyperalgesia, and primary and secondary mechanical hyperalgesia. Coadministration of topical L-menthol reduced spontaneous pain intensity (P < .01), neurogenic inflammation (P < .01), primary mechanical hyperalgesia (P < .05), secondary mechanical hyperalgesia (P < .05), and heat hyperalgesia (P < .05), but not cold hyperalgesia. L-menthol exhibited inhibitory effects on simultaneously established pain, hypersensitivity, and neurogenic inflammation in a human TRPA1-induced pain model. Potent TRPM8 agonists could be useful as topical antihyperalgesics. The study and the trial protocol is registered and approved by the local research ethics committee under the jurisdiction of the Danish Medicines Agency number N-20130005. The protocol also is registered at Clinicaltrials.gov under NCT02653703. ⋯ Drugs interacting with transient receptor potential channels are of great therapeutic potential. In the present study we established cutaneous pain and hyperalgesia using the TRPA1 agonist CA. Subsequently, we showed that the frequently used topical counterirritant and TRPM8 agonist, L-menthol, decreased evoked pain, hyperalgesia, and inflammation, indicating direct and indirect antinociceptive mechanisms.
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Endometriosis is a common cause of pain including radicular pain. Ectopic endometrial tissue may directly affect peripheral nerves including the sciatic, which has not been modelled in animals. ⋯ Some especially painful forms of endometriosis are essentially neuropathic, because peripheral nerves are directly affected by nearby ectopic endometrial tissue. We modelled endometriosis by implanting autologous uterine tissue around rat sciatic nerve. We observed mechanical and cold pain behaviours along with signs of inflammation and nerve damage and increased pro-inflammatory cytokines at the implant site. Pain behaviours correlated with signs of nerve inflammation and damage rather than with cyst survival.
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Randomized Controlled Trial
Effects of intraoperative high-dose vs low-dose remifentanil for postoperative epidural analgesia after gynecological abdominal surgery: a randomized clinical trial.
To evaluate whether intraoperative high-dose remifentanil infusion increased local anesthetic consumption in postoperative epidural analgesia and postoperative pain scores compared with low-dose remifentanil infusion. ⋯ Intraoperative high-dose remifentanil infusion increased local anesthetic consumption in postoperative epidural analgesia relative to low-dose remifentanil.
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To evaluate widespread pressure pain in patients with chronic plantar heel pain compared with that in healthy controls and to investigate the differences in ultrasound imaging and quality of life between these two groups. ⋯ Patients suffering from chronic plantar heel pain showed widespread and bilateral hypersensitivity, increased thickness of the plantar fascia in the affected foot, and deterioration in quality of life and physical functioning compared with matched controls.