Risperidone in analgesia induced by paracetamol and meloxicam in experimental pain

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the best therapeutic options to treat pain. Their use in combination with other drugs may broaden their applicability in analgesia if their ceiling and adverse effects are reduced. The aim of this study was to evaluate the pharmacological interaction of two NSAIDs, paracetamol and meloxicam, with the antipsychotic drug risperidone in mice, in several experimental tests of nociceptive and inflammatory pain. Antinociception was assessed by dose-response curves to paracetamol and meloxicam before and after the i.p. administration of 0.5 mg/kg of risperidone. Results are presented as means AE SEM and differences were calculated by one-way ANOVA followed by Tukey's post-test. Paracetamol and meloxicam produced a dose-related antinociceptive effect with diverse potencies. Risperidone increased the analgesia mediated by paracetamol and meloxicam only in the tonic tests that detected inflammatory pain. This suggests that COX inhibition is only a partial explanation of the increased analgesic potency of paracetamol and meloxicam since the effects of NSAIDs in the CNS are mediated by multiple mechanisms. These results indicate that the combination of risperidone with paracetamol or meloxicam could be a new and effective alternative for the management of inflammatory pain.

Can cannabidiol have an analgesic effect?

“…The authors showed that this action is mediated by an increase in the activity of both cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) which are major targets of non-steroidal anti-inflammatory drugs (NSAIDs). 90,91 In addition, CBD is an inhibitor of lipoxygenase (LOX), which is potentially involved in the production of inflammatory factors.. 92 The antiinflammatory effects of CBD have been repeatedly confirmed in preclinical observations. [93][94][95][96][97] An inhibitory effect on the cytochrome P450 superfamily (CYPs) constituting major enzymes involved in many drug metabolisms, including NSAIDs commonly used in pain management, has also been described.…”

“…Observations by Wheal et al conducted on a rat model sought a mechanism for the anti‐inflammatory and analgesic properties of CBD in preclinical models of diabetes. The authors showed that this action is mediated by an increase in the activity of both cyclooxygenase 1 (COX‐1) and cyclooxygenase 2 (COX‐2) which are major targets of non‐steroidal anti‐inflammatory drugs (NSAIDs) 90,91 . In addition, CBD is an inhibitor of lipoxygenase (LOX), which is potentially involved in the production of inflammatory factors.…”

Pharmacodynamic differences between racemic ibuprofen and dexibuprofen in murine preclinical study

“…administration of 1,0 mg/kg of naltrexone (NTX), or naltrindole (NTI) or norbinaltorphimine (nor-BNI), or 5 mg/kg of L-NAME, 0,5 mg/kg of risperidone (RISPER) or tropisetron (TROPI) in the WT assay, using at least 6-8 animals for each of at least 4 doses. The doses used were selected according to previously published studies [8,9] and adjusted according to preliminary experiments.…”

“…One of the most used is the acetic acid writhing test, which is a tonic visceral pain that mimics a type of human pain and uses a chemical stimulus, a dilution of acetic acid, to induce a characteristic behavior of pain. In this test, the chemical s t i m u l u s induces a wave of contraction of the abdominal muscle followed by extension of the hindlimbs (writhes) and reduction in motor activity [8][9].…”

Naphazoline and oxymetazoline are superior to epinephrine in enhancing the cutaneous analgesia of lidocaine in rats

“…Then, the curve was fitted by the computer-derived SAS NLIN Processes (SAS Institute Inc., Carey, NC) to derive the ED 50. [25,26] The ED 25 , ED 75 , and ED 95 were obtained by using the same method (SAS NLIN Processes) [27,28].…”