Abstract
Pharmacological treatment of inflammatory pain is usually done by administration of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs present high efficacy, although side effects are common, especially gastrointestinal lesions. One of the pharmacological strategies to minimize such effects is the combination of drugs and natural products with synergistic analgesic effect. The monoterpene terpinolene (TPL) is a chemical constituent of essential oils present in many plant species, which have pharmacological activities, such as analgesic and anti-inflammatory. The association of ineffective doses of TPL and diclofenac (DCF) (3.125 and 1.25 mg/kg po, respectively) presented antinociceptive and anti-inflammatory effects in the acute (0, 1, 2, 3, 4, 5 and 6 h, after treatment) and chronic (10 days) inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA) in the right hind paw of female Wistar rats (170-230 g, n=6-8). The mechanical hyperalgesia was assessed by the Randall Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethismography. The TPL/DCF association reduced neutrophils, macrophages and lymphocytes in the histological analysis of the paw, following a standard staining protocol with hematoxylin and eosin and the counts were performed with the aid of optical microscopy after chronic oral administration of these drugs. Moreover, the TPL/DCF association did not induce macroscopic gastric lesions. A possible mechanism of action of the analgesic effect is the involvement of 5-HT2A serotonin receptors, because ketanserin completely reversed the antinociceptive effect of the TPL/DCF association. These results suggest that the TPL/DCF association had a synergistic anti-inflammatory and analgesic effect without causing apparent gastric injury, and that the serotonergic system may be involved in the antinociceptive effect of this association.
Highlights
Inflammatory pain is characterized by an increased sensitivity of the injured tissue generated by the release of inflammatory mediators [1]
Sodium diclofenac (DCF) (Figure 1A) is a nonsteroidal anti-inflammatory drugs (NSAIDs) that acts by cyclooxygenase (COX) 1 and 2 inhibition, and it has been available in the medical arsenal for over 40 years, ranked as the eighth most sold drug in the world [3]
Based on the described benefits of NSAIDs, herbal drugs, or their combination, we evaluated the effect of the TPL, DCF and the association of both (TPL/DCF) on the complete Freund’s adjuvant (CFA)-induced inflammatory process, as well as the incidence of gastric damage
Summary
Inflammatory pain is characterized by an increased sensitivity of the injured tissue generated by the release of inflammatory mediators [1]. Pharmacological treatment of inflammatory pain is usually performed with nonsteroidal anti-inflammatory drugs (NSAIDs), which show high efficacy [2]. About 20% of individuals experience side effects during treatment with NSAIDs, including abdominal pain, heartburn and diarrhea [4]. The monoterpenes are extracted from several herbs and represent 90% of the essential oils constituents [5]. In relation to its pharmacological effects, 27 and 32 monoterpenes were found to have analgesic [6] and anti-inflammatory activities [7], respectively
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Schedule a callMore From: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
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