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. 2024;15(8):411-416.
doi: 10.30466/vrf.2024.2015987.4069. Epub 2024 Aug 15.

Effect of curcumin on formalin-induced muscle pain in male rats: role of local cyclooxygenase system

Nabat Naqshbandi  1 , Esmaeal Tamaddonfard  2 , Amir Erfanparast  2 , Farhad Soltanalinejad-Taghiabad  2
Affiliations

Effect of curcumin on formalin-induced muscle pain in male rats: role of local cyclooxygenase system

Nabat Naqshbandi et al. Vet Res Forum. 2024.

Abstract

Investigating the mechanisms responsible for pain processing of natural and synthetic chemical compounds is necessary to optimize pain management. Curcumin (Cur), the active ingredient of turmeric, exhibits potent analgesic and anti-inflammatory properties by employing multiple mechanisms at the local peripheral, spinal and supra-spinal levels. This study was aimed to investigate the effect of oral administration of Cur on muscle pain induced by intramuscular (IM) injection of formalin. To explore the possible local mechanisms, a cyclooxygenase (COX) inhibitor, diclofenac (Dic) and a COX product, prostaglandin E2 (PGE2), were applied. The IM injection of formalin (25.00 µL, 2.50%) into the gastrocnemius muscle induced two distinct phases of hind leg flinching. A short-lasting (10 min) hind leg lifting was observed following IM injection of PGE2 (2 µg kg-1, 25.00 µL). Oral administration of Cur (25.00 and 100 mg kg-1) and IM injection of 40.00 µg kg-1 Dic attenuated formalin and PGE2 induced nociceptive behaviors. Contra-lateral IM injection of Dic did not change muscle pain induced by ipsilateral IM injection of formalin and PGE2. The second phase of formalin induced flinching as well as PGE2 evoked lifting were more suppressed when 40.00 µg kg-1 Dic and 100 mg kg-1 Cur were used together. Locomotor activity was not changed by the above-mentioned treatments. It was concluded that the reducing effect of muscle pain of Cur might be related to the local inhibition of COX.

Keywords: Curcumin; Cyclooxygenase; Diclofenac; Muscle pain; Prostaglandin E2.

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Conflict of interest statement

No financial or other conflicts of interest are declared by the authors.

Figures

Fig. 1
Fig. 1
A) Time dependent hind leg flinching following intramuscular (IM) injection of normal saline and formalin 2.50% and B) Time-dependent hind leg lifting after IM injection of ethanol and 2.00 µg kg-1 prostaglandin E2 (PGE2). Normal saline and ethanol were IM administered one min before IM injection of formalin and PGE2, respectively. Values from each group are the mean ± SEM (n = 6). * p < 0.05, † p < 0.01, ‡ p < 0.001 in comparison with corresponding control group.
Fig. 2
Fig. 2
The effects of per os (PO) administration of distilled water (DW) and curcumin (Cur) at doses of 6.25, 25.00 and 100.00 mg kg-1 on A) first (1 - 5 min) and second (26 - 45 min) phases of hind leg flinching induced by intramuscular (IM) injection of formalin, and B) Hind leg lifting induced by IM injection of prostaglandin E2 (PGE2). The Cur was PO administered 45 min before IM injections of formalin and PGE2. Values from each group are the mean ± SEM (n = 6). † p < 0.01 and ‡ p < 0.001 in comparison with corresponding DW group.
Fig. 3
Fig. 3
The effects of ipsilateral (IL) and contralateral (CL) intramuscular (IM) injection of normal saline and 40.00 µg kg-1 diclofenac (Dic) on A) Formalin induced flinching number, and B) The PGE2-induced hind leg lifting duration. The Dic was IM administered one min before IM injections of formalin and PGE2. Values from each group are the mean ± SEM (n = 6). † p < 0.01 and ‡ p < 0.001 in comparison with normal saline group.
Fig. 4
Fig. 4
The effects of IM injection of 40.00 µg kg-1 diclofenac (Dic) after per os (PO) administration of distilled water (DW) and 100 mg kg-1 curcumin (Cur) on the A) First (1 - 5 min) and second (26 - 45 min) phases of hind leg flinching induced by intramuscular (IM) injection of formalin, and B) Hind leg lifting evoked by IM injection of prostaglandin E2 (PGE2). The Cur and Dic were PO and IM administered 45 and one min before IM injection of formalin and PGE2. Values from each group are the mean ± SEM (n = 6). ‡ p < 0.001 and # p < 0.0001 in comparison with corresponding DW group.
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