The Anti-Nociception Effect of Dezocine in a Rat Neuropathic Pain Model

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Abstract

The treatment of neuropathic pain (NP) currently remains clinically challenging. In an attempt to identify novel targets of known opioids, we found that dezocine, a non-addictive opioid, inhibits norepinephrine and serotonin reuptake through their transporter proteins which open the potential for dezocine to manage NP. In the present study, the effect of dezocine on NP was observed in a rat model of chronic constriction injury (CCI). The paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) were used to evaluate thermal hyperalgesia and mechanic allodynia for nociceptive response. PWL and PWT tests were performed at 11:00 AM starting from 1 day before CCI surgery and 1, 3, 7, 10 days after right sciatic nerve ligation in the presence or absence of daily intraperitoneal injection of dezocine. The results demonstrated that the CCI-induced thermal and mechanical pain hypersensitivity was attenuated by dezocine significantly and persistently without sign of tolerance, indicating that dezocine could be an alternative medication for the treatment of NP. Clinical trial to confirm such discovery is warranted.

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Most cited references 35

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A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia.

Mark Brown, Sonia Flores, R Dubner … (1987)

A method to measure cutaneous hyperalgesia to thermal stimulation in unrestrained animals is described. The testing paradigm uses an automated detection of the behavioral end-point; repeated testing does not contribute to the development of the observed hyperalgesia. Carrageenan-induced inflammation resulted in significantly shorter paw withdrawal latencies as compared to saline-treated paws and these latency changes corresponded to a decreased thermal nociceptive threshold. Both the thermal method and the Randall-Selitto mechanical method detected dose-related hyperalgesia and its blockade by either morphine or indomethacin. However, the thermal method showed greater bioassay sensitivity and allowed for the measurement of other behavioral parameters in addition to the nociceptive threshold.

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A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man.

Gary Bennett, Y. Xie (1988)

A peripheral mononeuropathy was produced in adult rats by placing loosely constrictive ligatures around the common sciatic nerve. The postoperative behavior of these rats indicated that hyperalgesia, allodynia and, possibly, spontaneous pain (or dysesthesia) were produced. Hyperalgesic responses to noxious radiant heat were evident on the second postoperative day and lasted for over 2 months. Hyperalgesic responses to chemogenic pain were also present. The presence of allodynia was inferred from the nocifensive responses evoked by standing on an innocuous, chilled metal floor or by innocuous mechanical stimulation, and by the rats' persistence in holding the hind paw in a guarded position. The presence of spontaneous pain was suggested by a suppression of appetite and by the frequent occurrence of apparently spontaneous nocifensive responses. The affected hind paw was abnormally warm or cool in about one-third of the rats. About one-half of the rats developed grossly overgrown claws on the affected side. Experiments with this animal model may advance our understanding of the neural mechanisms of neuropathic pain disorders in humans.

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Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain.

E S J Arnér, B Meyerson (1988)

The aim of the present study has been to assess the responsiveness of various types of chronic pain to opioids given i.v. and tested against placebo in a double-blind, randomized fashion. Pain classified as primary nociceptive was effectively alleviated (P greater than 0.001) while neuropathic deafferentation pain was not significantly influenced by morphine or equivalent doses of other opioids. Also 'idiopathic' pain, defined as chronic pain with no or little demonstrable pathology, failed to respond. The results were not related to whether the patients were regular users of narcotic analgesics or not. The outcome of our double-blind opioid test has proved useful to justify a continued, or discontinued, use of narcotic medication in individual patients. It may also support the indication and choice of invasive stimulation procedures (spinal cord or brain). The results of the study illustrate the misconception of chronic pain as an entity and highlight the importance of recognizing different neurobiological mechanisms and differences in responsiveness to analgesic drugs as well as to non-pharmacological modes of treatment. The opioid test has thus become a valuable tool in pain analysis and helpful as a guide for further treatment.

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Author and article information

Journal

Journal ID (nlm-journal-id): 101638640

Journal ID (pubmed-jr-id): 42946

Journal ID (nlm-ta): Transl Perioper Pain Med

Journal ID (iso-abbrev): Transl Perioper Pain Med

Title: Translational perioperative and pain medicine

ISSN (Electronic): 2330-4871

Publication date Nihms-submitted: 10 August 2014

Publication date (Print): 2014

Publication date PMC-release: 27 October 2014

Volume: 1

Issue: 1

Pages: 5-8

Affiliations

[1 ]Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia PA 19104, USA

[2 ]Department of Anesthesiology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, China

Author notes

Corresponding author: Renyu Liu, M.D., Ph.D. Assistant Professor. Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Address: 336 John Morgan building, 3620 Hamilton Walk, Philadelphia PA, 19104 USA., Phone: 2156623750, Fax: 2153495078 liur@ 123456uphs.upenn.edu . Weifeng Wu, MD, PhD, Professor and Chair, Department of Anesthesia & Intensive Care, Eastern Hepatobiliary Surgical Hospital, Address: The Second Military Medical University, Shanghai, 200438, China. Phone: 86-21-55063846, Fax: 86-21-25070783 ywf808@ 123456sohu.com

Article

Manuscript ID: NIHMS618424

PMC ID: 4209404

PubMed ID: 25356434

SO-VID: f9c0a8cb-2913-419b-b77a-a27790764794

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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

The Anti-Nociception Effect of Dezocine in a Rat Neuropathic Pain Model

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Most cited references 35

A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia.

A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man.

Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain.

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