Spontaneous Pain-Like Behaviors Are More Sensitive to Morphine and Buprenorphine Than Mechanically Evoked Behaviors in a Rat Model of Acute Postoperative Pain

Kabadi, Rajiv; Kouya, Francois; Cohen, Hillel W.; Banik, Ratan K.

doi:10.1213/ane.0000000000000571

Cited by 23Pain Mechanisms and TreatmentsAnesthesia and Pain ManagementVeterinary Pharmacology and Anesthesia

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Spontaneous Pain-Like Behaviors Are More Sensitive to Morphine and Buprenorphine Than Mechanically Evoked Behaviors in a Rat Model of Acute Postoperative Pain

Kabadi, Rajiv, Kouya, Francois, Cohen, Hillel W., Banik, Ratan K.·2015·Anesthesia & Analgesia

DOI 10.1213/ane.0000000000000571

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Abstract

BACKGROUND: Nonevoked spontaneous pain is most problematic for postoperative patients. Physicians assess this form of pain using the human visual analog scale or verbal numeric rating scale. Recent studies have proposed that spontaneous foot-lifting (SFL) behaviors are an expression of spontaneous pain in animals after spinal nerve injury or adjuvant-induced inflammation. In the current study, we characterize SFL behaviors in a rat model of acute postoperative pain, which includes comparisons with evoked behaviors to analgesic treatments. METHODS: SFL was manually recorded over four 5-minute periods with 10-minute intervals between each testing session. Paw-withdrawal thresholds were subsequently measured with an electronic von Frey esthesiometer. To evaluate the effects of age, rats were tested in different age groups: 2, 7, and >26 months. The effects of buprenorphine and morphine were tested in a separate group of animals, which received intraperitoneal injections of saline, morphine (0.01, 0.1, 1, or 2 mg/kg), or buprenorphine (0.001, 0.01, or 0.1 mg/kg) before testing. RESULTS: SFL behaviors peaked at 3 hours after incision and significantly recovered by the 3rd or 4th postoperative day (P < 0.0001). The presentation of these behaviors did not significantly vary with animal age (2, 7, and >26 months old; P = 0.30). SFL behaviors, with the exception of rapid SFL at 3 hours after incision, did not show significant correlation with paw-withdrawal threshold behaviors. The median effective dose of buprenorphine for reversal of mechanical hyperalgesia (0.0452 mg/kg; 95% CI, 0.0259-0.0787) was significantly larger than for reversing rapid (0.0027 mg/kg; 95% CI, 0.0009-0.0083; P < 0.0001) and prolonged (0.0004 mg/kg, 95% CI, 0.0000, 0.0035; P = 0.001) SFL at 3 hours after incision. Similarly, the median effective dose of morphine for reversal of mechanical hypersensitivity behaviors (2.901 mg/kg; 95% CI, 1.132-7.436) was larger than for SFL count (0.4044 mg/kg; 95% CI, 0.1048-1.561; P = 0.0103) and SFL duration (0.0309 mg/kg; 95% CI, 0.0095-0.0998; P < 0.0001) at 3 hours after incision. CONCLUSIONS: The present study demonstrates that a hindpaw plantar incision induces SFL behaviors in rats and that these behaviors have higher bioassay sensitivity to analgesic interventions with morphine and buprenorphine compared with mechanically evoked behaviors.

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Authors: Kabadi, R., Kouya, F., Cohen, H. W., & Banik, R. K.
Affiliations: Seton Hall University (US)
Albert Einstein College of Medicine (US)
Corresponding author: Kabadi, Rajiv
Banik, Ratan K.
ORCID: Kabadi, Rajiv
Cohen, Hillel W.
Banik, Ratan K.
Venue: Anesthesia & Analgesia
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2015-02
Volume: 120
Issue: 2
Pages: 472-478
ISSN: 0003-2999 (ISSN-L)
DOI: 10.1213/ane.0000000000000571
OpenAlex: W2056639815
Cited by: 23
References: 15
Citations by year: 2026: 1 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 1
FWCI: 0.89
Type: journal article
Language: en
Open access: closed
Locations: Anesthesia & Analgesia (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (KL2TR001071, TL1TR001072, UL1TR001073)
National Institute on Aging (AG030352, AG030352-02S2, R21AG030352)
National Center for Advancing Translational Sciences
Topics: Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Pain Management
Health Sciences › Veterinary › Small Animals › Veterinary Pharmacology and Anesthesia
Keywords: spontaneous pain, postoperative pain, morphine, buprenorphine, analgesic efficacy, paw withdrawal threshold, mechanical hyperalgesia, age effects, rat model, postoperative analgesia, opioid dose-response, adjuvant-induced inflammation, spinal nerve injury, visceral pain, visceral hypersensitivity
MeSH terms: Aging, Analgesics, Opioid, Animals, Behavior, Animal, Buprenorphine, Hyperalgesia, Morphine, Postoperative Pain, Physical Stimulation, Rats, Inbred F344, Species Specificity, Rats, Sprague-Dawley, Rats, Acute Pain

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Spontaneous Pain-Like Behaviors Are More Sensitive to Morphine and Buprenorphine Than Mechanically Evoked Behaviors in a Rat Model of Acute Postoperative Pain

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