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Antinociceptive and Abuse Potential Effects of Cannabinoid/Opioid Combinations in a Chronic Pain Model in Rats.
Brain Sci. 2019 Nov 17; 9(11)BS

Abstract

Chronic pain is a persistent and debilitating health problem. Although the use of analgesics such as opioids is useful in mitigating pain, their prolonged use is associated with unwanted effects including abuse liability. This study assesses the antinociceptive effect of combining subtherapeutic doses of two opioids (morphine or tramadol) with the synthetic cannabinoid CP55940 (2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan -2-yl)phenol). It also evaluates the associated adverse effects of these drugs and combinations. Adult male rats were injected with intraplantar complete Freund's adjuvant (CFA) to produce mechanical allodyia. Antinociceptive effect of morphine, tramadol, the synthetic cannabinoid CP55940, or their combinations was evaluated three to nine days post-CFA injections. Intracranial self-stimulation (ICSS) was utilized to evaluate the abuse liability of these drugs or their combinations. All drugs alone produced a dose-dependent antinociceptive effect. Morphine produced minimal effect on ICSS, but both tramadol and CP55940 produced dose-dependent depression of ICSS. Morphine at a dose of 0.32 mg/kg enhanced the antinociceptive effects of CP55940, in that, CP55940 produced antinociception at a lower dose (0.1 mg/kg) when compared to the vehicle. The aforementioned combinations did not change CP55940-induced depression of ICSS. On the other hand, tramadol failed to enhance the antinociceptive effect of CP55940. Our data suggest that combining CP55940 with morphine, but not tramadol, shows a better antinociceptive profile with no additional risk of abuse liability, which represents a potential pain management approach.

Authors+Show Affiliations

Faculty of Medicine, The University of Jordan, Amman 11942, Jordan.Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan.Faculty of Pharmacy, Philadelphia University, Amman 19392, Jordan.Faculty of Clinical Pharmacy, King Faisal University, Hofuf 31982, Saudi Arabia.Faculty of Medicine, The University of Jordan, Amman 11942, Jordan.Faculty of Medicine, The University of Jordan, Amman 11942, Jordan.Faculty of Medicine, The Hashemite University, Zarqa 13133, Jordan.Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31744226

Citation

Alsalem, Mohammad, et al. "Antinociceptive and Abuse Potential Effects of Cannabinoid/Opioid Combinations in a Chronic Pain Model in Rats." Brain Sciences, vol. 9, no. 11, 2019.
Alsalem M, Altarifi A, Haddad M, et al. Antinociceptive and Abuse Potential Effects of Cannabinoid/Opioid Combinations in a Chronic Pain Model in Rats. Brain Sci. 2019;9(11).
Alsalem, M., Altarifi, A., Haddad, M., Aldossary, S. A., Kalbouneh, H., Aldaoud, N., Saleh, T., & El-Salem, K. (2019). Antinociceptive and Abuse Potential Effects of Cannabinoid/Opioid Combinations in a Chronic Pain Model in Rats. Brain Sciences, 9(11). https://doi.org/10.3390/brainsci9110328
Alsalem M, et al. Antinociceptive and Abuse Potential Effects of Cannabinoid/Opioid Combinations in a Chronic Pain Model in Rats. Brain Sci. 2019 Nov 17;9(11) PubMed PMID: 31744226.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antinociceptive and Abuse Potential Effects of Cannabinoid/Opioid Combinations in a Chronic Pain Model in Rats. AU - Alsalem,Mohammad, AU - Altarifi,Ahmad, AU - Haddad,Mansour, AU - Aldossary,Sara A, AU - Kalbouneh,Heba, AU - Aldaoud,Nour, AU - Saleh,Tareq, AU - El-Salem,Khalid, Y1 - 2019/11/17/ PY - 2019/10/12/received PY - 2019/11/04/revised PY - 2019/11/14/accepted PY - 2019/11/21/entrez PY - 2019/11/21/pubmed PY - 2019/11/21/medline KW - CP55940 KW - chronic pain KW - complete Freund’s adjuvant (CFA) KW - intracranial self-stimulation (ICSS) KW - morphine KW - tramadol KW - von Frey JF - Brain sciences JO - Brain Sci VL - 9 IS - 11 N2 - Chronic pain is a persistent and debilitating health problem. Although the use of analgesics such as opioids is useful in mitigating pain, their prolonged use is associated with unwanted effects including abuse liability. This study assesses the antinociceptive effect of combining subtherapeutic doses of two opioids (morphine or tramadol) with the synthetic cannabinoid CP55940 (2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan -2-yl)phenol). It also evaluates the associated adverse effects of these drugs and combinations. Adult male rats were injected with intraplantar complete Freund's adjuvant (CFA) to produce mechanical allodyia. Antinociceptive effect of morphine, tramadol, the synthetic cannabinoid CP55940, or their combinations was evaluated three to nine days post-CFA injections. Intracranial self-stimulation (ICSS) was utilized to evaluate the abuse liability of these drugs or their combinations. All drugs alone produced a dose-dependent antinociceptive effect. Morphine produced minimal effect on ICSS, but both tramadol and CP55940 produced dose-dependent depression of ICSS. Morphine at a dose of 0.32 mg/kg enhanced the antinociceptive effects of CP55940, in that, CP55940 produced antinociception at a lower dose (0.1 mg/kg) when compared to the vehicle. The aforementioned combinations did not change CP55940-induced depression of ICSS. On the other hand, tramadol failed to enhance the antinociceptive effect of CP55940. Our data suggest that combining CP55940 with morphine, but not tramadol, shows a better antinociceptive profile with no additional risk of abuse liability, which represents a potential pain management approach. SN - 2076-3425 UR - https://www.unboundmedicine.com/medline/citation/31744226/Antinociceptive_and_Abuse_Potential_Effects_of_Cannabinoid/Opioid_Combinations_in_a_Chronic_Pain_Model_in_Rats_ L2 - http://www.mdpi.com/resolver?pii=brainsci9110328 DB - PRIME DP - Unbound Medicine ER -
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