Differences in the sensitivity of behavioural measures of pain to the selectivity of cyclo‐oxygenase inhibitors

Abstract

Changes in paw pressure threshold seem to best reflect the anti-hyperalgesic properties of COX-inhibitors with enough sensitivity to enable estimation of the dose-exposure-response curve.

Inflammation-induced decrease in voluntary wheel running in mice: A nonreflexive test for evaluating inflammatory pain and analgesia

“…This difference cannot be attributed to the possible ameliorative effects of the running activity itself on inflammatory pain, since mice not submitted to voluntary wheel running during the first days after CFA injection do not show any alteration in the speed of recovery of wheel running performance. In addition, changes in hindpaw weight-bearing (another non-reflexive outcome) in mice not submitted to any form of exercise were also much shorter-lasting than mechanical allodynia, as previously described in the rat [15,47], and followed a similar time-course to the recovery in voluntary wheel running. These results indicate that the difference in the time-course of these outcomes cannot be explained by effects of physical activity and that the presence of a pronounced mechanical allodynia in the hindlimb does not necessarily induce a significant impairment in voluntary performance.…”

“…There is no agreement on whether changes in hindpaw weight-bearing reflect spontaneous pain [2], increased touch sensitivity of the injured foot [15], or pain-avoidance behavior [26]. Similarly, voluntary wheel running could be affected by a decreased willingness to perform the task due to ongoing pain or by the pain induced by movement/impact (mechanical hypersensitivity) of the inflamed tissue during or after the performance of the target behavior.…”

“…To this end, we characterized the degree and time-course of changes in locomotion, using running wheels, in mice with experimentally inflamed hindpaws and compared this with commonly-used measures of inflammatory pain: changes in weight-bearing [15] and punctate mechanical hypersensitivity measured with von Frey hairs, a widely used outcome measure in chronic pain models [24,25]. We then pharmacologically characterized the restoration of the peripheral inflammation-induced decrease in voluntary wheel running, using a representative set of drugs of various chemical and pharmacological classes currently used as therapeutics in humans, including the non-selective non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen, naproxen and diclofenac [16], the selective cyclooxygenase (COX)-2 inhibitor celecoxib [23,38], the corticosteroid prednisolone [11,17], and the opioid morphine [46].…”

Pharmacokinetic-Pharmacodynamic Modeling of the Inhibitory Effects of Naproxen on the Time-Courses of Inflammatory Pain, Fever, and the Ex Vivo Synthesis of TXB2 and PGE2 in Rats

“…Preclinical models that increase confidence of clinical efficacy are not always similar to models that give detailed information on potency, intrinsic activity, timecourse of the effect, and dose and time dependencies such as saturation, tolerance, and sensitization (1,(4)(5)(6). With respect to in vivo pain models, it is challenging to differentiate compounds based on their analgesic efficacy due to substantial pharmacodynamic variability and limitations in measuring frequencies of both effect and exposure within an individual.…”

Neuroprotective mechanism of losartan and its interaction with nimesulide against chronic fatigue stress

“…Nimesulide is a preferential COX-2 inhibitor having potent antiinflammatory, antipyretic and analgesic properties (Huntjens et al 2009). It has also been shown to attenuate microglia and astrocyte activation in various neurological studies (Sagar et al 2011).…”