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Effects of the combined oral administration of NSAIDs and dextromethorphan on behavioral symptoms indicative of arthritic pain in rats.
Pain. 1996 Nov; 68(1):119-27.PAIN

Abstract

The effects of combined single oral treatments with non-steroidal anti-inflammatory drugs (NSAIDs) and the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dextromethorphan (DM) on arthritic pain were examined in a rat model of adjuvant-induced arthritis. Although 12.5-100 mg/kg doses of DM alone produced no reliable effects, treatments with ibuprofen (IB, 50 and 100 mg/kg but not 12.5 or 25 mg/kg) produced mild analgesia in arthritic rats as determined using the Randall-Sellito test. IB showed a dose-response relationship which appeared to plateau at doses of 50 and 100 mg/kg. Adding 50 mg/kg DM to each IB dose resulted in significantly greater analgesic activity than IB alone at doses of 25, 50 and 100 mg/kg. A similar interaction between 50 mg/kg DM and 50 mg/kg IB occurred with respect to spontaneous pain behavior. Adding 25 mg/kg DM to 25 mg/kg IB likewise increased analgesia as measured by both the Randall-Sellito and spontaneous pain behavior tests (both P < 0.05). Five more NSAIDs were evaluated using the Randall-Sellito test, which included naproxen (NP), piroxicam (PIR), etodolac (ET), diclofenac (DC), and ketorolac (KE). For all six NSAIDS, the addition of 50 mg/kg DM reliably increased their analgesic potency, as indicated by reliable increases in previously effective NSAID doses (all six NSAIDs) as well as previously ineffective NSAID doses (IB, NP, DC, and PIR). These data demonstrate that DM greatly potentiates the analgesic activity of IB, DC, NP, PIR, ET, and KT and increases the peak effect over the NSAIDs alone. Similiar to DM's previously demonstrated enhancement of opioid analgesia in acute pain, the combination of DM and an NSAID may represent a novel analgesic approach to improved management of arthritic pain.

Authors+Show Affiliations

Department of Anesthesiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9252006

Citation

Price, D D., et al. "Effects of the Combined Oral Administration of NSAIDs and Dextromethorphan On Behavioral Symptoms Indicative of Arthritic Pain in Rats." Pain, vol. 68, no. 1, 1996, pp. 119-27.
Price DD, Mao J, Lu J, et al. Effects of the combined oral administration of NSAIDs and dextromethorphan on behavioral symptoms indicative of arthritic pain in rats. Pain. 1996;68(1):119-27.
Price, D. D., Mao, J., Lu, J., Caruso, F. S., Frenk, H., & Mayer, D. J. (1996). Effects of the combined oral administration of NSAIDs and dextromethorphan on behavioral symptoms indicative of arthritic pain in rats. Pain, 68(1), 119-27.
Price DD, et al. Effects of the Combined Oral Administration of NSAIDs and Dextromethorphan On Behavioral Symptoms Indicative of Arthritic Pain in Rats. Pain. 1996;68(1):119-27. PubMed PMID: 9252006.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of the combined oral administration of NSAIDs and dextromethorphan on behavioral symptoms indicative of arthritic pain in rats. AU - Price,D D, AU - Mao,J, AU - Lu,J, AU - Caruso,F S, AU - Frenk,H, AU - Mayer,D J, PY - 1996/11/1/pubmed PY - 1996/11/1/medline PY - 1996/11/1/entrez SP - 119 EP - 27 JF - Pain JO - Pain VL - 68 IS - 1 N2 - The effects of combined single oral treatments with non-steroidal anti-inflammatory drugs (NSAIDs) and the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dextromethorphan (DM) on arthritic pain were examined in a rat model of adjuvant-induced arthritis. Although 12.5-100 mg/kg doses of DM alone produced no reliable effects, treatments with ibuprofen (IB, 50 and 100 mg/kg but not 12.5 or 25 mg/kg) produced mild analgesia in arthritic rats as determined using the Randall-Sellito test. IB showed a dose-response relationship which appeared to plateau at doses of 50 and 100 mg/kg. Adding 50 mg/kg DM to each IB dose resulted in significantly greater analgesic activity than IB alone at doses of 25, 50 and 100 mg/kg. A similar interaction between 50 mg/kg DM and 50 mg/kg IB occurred with respect to spontaneous pain behavior. Adding 25 mg/kg DM to 25 mg/kg IB likewise increased analgesia as measured by both the Randall-Sellito and spontaneous pain behavior tests (both P < 0.05). Five more NSAIDs were evaluated using the Randall-Sellito test, which included naproxen (NP), piroxicam (PIR), etodolac (ET), diclofenac (DC), and ketorolac (KE). For all six NSAIDS, the addition of 50 mg/kg DM reliably increased their analgesic potency, as indicated by reliable increases in previously effective NSAID doses (all six NSAIDs) as well as previously ineffective NSAID doses (IB, NP, DC, and PIR). These data demonstrate that DM greatly potentiates the analgesic activity of IB, DC, NP, PIR, ET, and KT and increases the peak effect over the NSAIDs alone. Similiar to DM's previously demonstrated enhancement of opioid analgesia in acute pain, the combination of DM and an NSAID may represent a novel analgesic approach to improved management of arthritic pain. SN - 0304-3959 UR - https://www.unboundmedicine.com/medline/citation/9252006/Effects_of_the_combined_oral_administration_of_NSAIDs_and_dextromethorphan_on_behavioral_symptoms_indicative_of_arthritic_pain_in_rats_ DB - PRIME DP - Unbound Medicine ER -