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Blockade of IL-18 signaling diminished neuropathic pain and enhanced the efficacy of morphine and buprenorphine.

Buprenorphine Research (PubMed) - Fri, 01/15/2016 - 8:30am

Blockade of IL-18 signaling diminished neuropathic pain and enhanced the efficacy of morphine and buprenorphine.

Mol Cell Neurosci. 2016 Jan 4;

Authors: Pilat D, Piotrowska A, Rojewska E, Jurga A, Ślusarczyk J, Makuch W, Basta-Kaim A, Przewlocka B, Mika J

Abstract
Currently, the low efficacy of antinociceptive drugs for the treatment of neuropathic pain is a major therapeutic problem. Here, we show the potential role of interleukin (IL)-18 signaling in this phenomenon. IL-18 is an important molecule that performs various crucial functions, including the alteration of nociceptive transmission in response to neuropathic pain. We have studied the changes in the mRNA and protein levels (qRT-PCR and Western blot analysis, respectively) of IL-18, IL-18-binding protein (IL-18BP) and the IL-18 receptor (IL-18R) over time in rats following chronic constriction injury (CCI) of the sciatic nerve. Our study demonstrated that the spinal levels of IL-18BP were slightly downregulated at days 7 and 14 in the rats subjected to CCI. In contrast, the IL-18 and IL-18R mRNA expression and protein levels were elevated in the ipsilateral spinal cord on days 2, 7 and 14. Moreover, in rats exposed to a single intrathecal administration of IL-18BP (50 and 100ng) 7 or 14days following CCI, symptoms of neuropathic pain were attenuated, and the analgesia pursuant to morphine and buprenorphine (0.5 and 2.5μg) was enhanced. In summary, the restoration of the analgesic activity of morphine and buprenorphine via the blockade of IL-18 signaling suggests that increased IL-18 pathway may account for the decreased analgesic efficacy of opioids for neuropathic pain.

PMID: 26763728 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Femoral and sciatic nerve blockades and incision site infiltration in rabbits undergoing stifle joint arthrotomy.

Buprenorphine Research (PubMed) - Fri, 01/15/2016 - 8:30am

Femoral and sciatic nerve blockades and incision site infiltration in rabbits undergoing stifle joint arthrotomy.

Lab Anim. 2016 Jan 12;

Authors: Kluge K, Larenza Menzies MP, Kloeppel H, Pearce SG, Bettschart-Wolfensberger R, Kutter AP

Abstract
This study was designed to determine whether perineural injections of local anaesthetics decreases intraoperative nociception and improves postoperative analgesia in New Zealand White rabbits undergoing experimental stifle arthrotomy. All animals were anaesthetized using isoflurane and received morphine intramuscularly. The sciatic and femoral nerves of the leg to be operated on were located using a nerve stimulator (1 Hz, 0.5 mA). Rabbits were assigned to a treatment group (LB; n = 12) or a placebo group (P; n = 12) in a randomized blinded fashion. Group LB received lidocaine 2% (1 mg/kg) combined with bupivacaine 0.5% (0.25 mg/kg) injections around the sciatic and femoral nerves (0.1 mL/kg total volume per site) and subcutaneous infiltration of the incision site with lidocaine 1% (1.25 mg/kg). Group P received the same volume of 0.9% NaCl. Rabbits in group P required higher doses of intraoperative fentanyl and propofol to reduce heart rate and suppress increase in systolic blood pressure, and maintain an adequate anaesthetic plane. Interventional analgesia (buprenorphine and carprofen) was required significantly earlier in rabbits in group P (2 and 6 h after the first nerve blockade, respectively) based on assessment of their pain-related behaviour and range of motion. Using a visual analogue scale (0 mm= no pain to 100 mm= maximal possible pain), rabbits in group LB were judged to show significantly less pain compared with rabbits in group P (14 ± 10 mm and 37 ± 25 mm, respectively) 2 h after nerve blockade. In conclusion, this technique of perineural analgesia combined with incision site infiltration reduced intraoperative fentanyl requirements and improved postoperative analgesia in rabbits.

PMID: 26763491 [PubMed - as supplied by publisher]

Categories: Bup Feeds

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