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Antihypersensitivity effects of tramadol hydrochloride in a rat model of postoperative pain.
Anesth Analg. 2012 Aug; 115(2):443-9.A&A

Abstract

BACKGROUND

Tramadol is used to treat a wide range of acute and chronic pain. This drug induces analgesia by 2 mechanisms of action: opioid receptor activation and enhancement of noradrenaline (NA) and serotonin (5-HT) transmission. The effect of tramadol on NA and 5-HT concentrations in the spinal cord, however, have not been assessed. In the present study, we investigated the antihypersensitivity effect of tramadol using a rat model of postoperative pain. We also evaluated the increase in NA and 5-HT levels in the spinal cord after tramadol injection using in vivo microdialysis.

METHODS

We made a hindpaw incision in male Sprague-Dawley rats (postoperative pain model). Tramadol was administered intraperitoneally and intrathecally 24 hours after paw incision. Mechanical hypersensitivity was measured by determining the withdrawal threshold using von Frey filaments. Microdialysis studies from the dorsal horn of the lumbar spinal cord were performed to measure NA and 5-HT levels after intraperitoneal injection of tramadol. We also measured the NA and 5-HT content in the spinal cord in normal rats and rats with paw incision.

RESULTS

Intraperitoneal (10, 20, and 40 mg/kg) and intrathecal (125, 250, and 500 μg) injection of tramadol produced an antihyperalgesic effect in a dose-dependent manner. The antihypersensitivity effect of tramadol was prevented by intrathecal pretreatment with methysergide (30 μg), a serotonin receptor antagonist; idazoxane (30 μg), a noradrenaline receptor antagonist; and naloxone (30 μg), a nonselective opioid receptor antagonist. Microdialysis study revealed that 5-HT and NA concentrations at the spinal dorsal horn were increased, peaking at 30 minutes after intraperitoneal injection of 20 mg/kg tramadol. Furthermore, the NA and 5-HT content in the ipsilateral dorsal half of the lumbar spinal cord was increased 1 day and 3 days after paw incision, respectively.

CONCLUSIONS

These findings indicate that tramadol inhibits postoperative hypersensitivity by increasing NA and 5-HT levels in the spinal cord and activating opioid receptors. Tramadol might be more effective in the early postoperative period when spinal NA and 5-HT levels are increased.

Authors+Show Affiliations

Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22, Showa, Maebashi, Gunma 371-8511, Japan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22575568

Citation

Kimura, Masafumi, et al. "Antihypersensitivity Effects of Tramadol Hydrochloride in a Rat Model of Postoperative Pain." Anesthesia and Analgesia, vol. 115, no. 2, 2012, pp. 443-9.
Kimura M, Obata H, Saito S. Antihypersensitivity effects of tramadol hydrochloride in a rat model of postoperative pain. Anesth Analg. 2012;115(2):443-9.
Kimura, M., Obata, H., & Saito, S. (2012). Antihypersensitivity effects of tramadol hydrochloride in a rat model of postoperative pain. Anesthesia and Analgesia, 115(2), 443-9. https://doi.org/10.1213/ANE.0b013e31825683c3
Kimura M, Obata H, Saito S. Antihypersensitivity Effects of Tramadol Hydrochloride in a Rat Model of Postoperative Pain. Anesth Analg. 2012;115(2):443-9. PubMed PMID: 22575568.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antihypersensitivity effects of tramadol hydrochloride in a rat model of postoperative pain. AU - Kimura,Masafumi, AU - Obata,Hideaki, AU - Saito,Shigeru, Y1 - 2012/05/10/ PY - 2012/5/12/entrez PY - 2012/5/12/pubmed PY - 2012/10/10/medline SP - 443 EP - 9 JF - Anesthesia and analgesia JO - Anesth Analg VL - 115 IS - 2 N2 - BACKGROUND: Tramadol is used to treat a wide range of acute and chronic pain. This drug induces analgesia by 2 mechanisms of action: opioid receptor activation and enhancement of noradrenaline (NA) and serotonin (5-HT) transmission. The effect of tramadol on NA and 5-HT concentrations in the spinal cord, however, have not been assessed. In the present study, we investigated the antihypersensitivity effect of tramadol using a rat model of postoperative pain. We also evaluated the increase in NA and 5-HT levels in the spinal cord after tramadol injection using in vivo microdialysis. METHODS: We made a hindpaw incision in male Sprague-Dawley rats (postoperative pain model). Tramadol was administered intraperitoneally and intrathecally 24 hours after paw incision. Mechanical hypersensitivity was measured by determining the withdrawal threshold using von Frey filaments. Microdialysis studies from the dorsal horn of the lumbar spinal cord were performed to measure NA and 5-HT levels after intraperitoneal injection of tramadol. We also measured the NA and 5-HT content in the spinal cord in normal rats and rats with paw incision. RESULTS: Intraperitoneal (10, 20, and 40 mg/kg) and intrathecal (125, 250, and 500 μg) injection of tramadol produced an antihyperalgesic effect in a dose-dependent manner. The antihypersensitivity effect of tramadol was prevented by intrathecal pretreatment with methysergide (30 μg), a serotonin receptor antagonist; idazoxane (30 μg), a noradrenaline receptor antagonist; and naloxone (30 μg), a nonselective opioid receptor antagonist. Microdialysis study revealed that 5-HT and NA concentrations at the spinal dorsal horn were increased, peaking at 30 minutes after intraperitoneal injection of 20 mg/kg tramadol. Furthermore, the NA and 5-HT content in the ipsilateral dorsal half of the lumbar spinal cord was increased 1 day and 3 days after paw incision, respectively. CONCLUSIONS: These findings indicate that tramadol inhibits postoperative hypersensitivity by increasing NA and 5-HT levels in the spinal cord and activating opioid receptors. Tramadol might be more effective in the early postoperative period when spinal NA and 5-HT levels are increased. SN - 1526-7598 UR - https://www.unboundmedicine.com/medline/citation/22575568/Antihypersensitivity_effects_of_tramadol_hydrochloride_in_a_rat_model_of_postoperative_pain_ L2 - https://doi.org/10.1213/ANE.0b013e31825683c3 DB - PRIME DP - Unbound Medicine ER -