Rofecoxib attenuates both primary and secondary inflammatory hyperalgesia: a randomized, double blinded, placebo controlled crossover trial in the UV-B pain model

Abstract

The analysis of drug's influence on peripheral and central sensitisation can give useful information about its mode of action and can lead to more efficacy in the treatment of pain. Peripheral inflammation is associated with peripheral expression and up-regulation of cyclooxygenase 2 (COX-2) in the CNS. The relative contribution of COX-2 mediated central sensitisation may be prominent under inflammatory conditions. In this randomized, double blinded, placebo controlled cross-over trial the effects of multidoses of the COX-2 selective inhibitor rofecoxib on primary and secondary hyperalgesia were evaluated in the UVB pain model. Twenty-four hours after local UVB irradiation at the upper leg of 42 healthy volunteers heat pain perception (HPPT) and heat pain tolerance thresholds (HPTT) were assessed within the inflammation. The area of secondary hyperalgesia was determined by pin prick test. Subjects received oral rofecoxib 50, 250, 500 mg or placebo. Pain testing was repeated after 3 and 6 h. Compared to placebo, rofecoxib significantly increased HPPT (1.55 and 1.08 degrees C, P<0.0001 and P=0.0333), HPTT (1.74 and 1.58 degrees C, P<0.0001 and P<0.0001), and reduced the mean area of secondary hyperalgesia by 15.6% (P=0.007) and 16.8% (P<0.001) after 3 and 6 h. No significant difference between the three dosage groups was observed. These data confirm peripheral effects of rofecoxib in a human inflammatory UV-B pain model and provide circumstantial evidence that even a standard clinical dose of rofecoxib reduces central hyperalgesia in inflammatory pain. We confirm that the effect of single oral dose of rofecoxib plateaus at 50 mg.

COX2 in CNS neural cells mediates mechanical inflammatory pain hypersensitivity in mice

“…This contrasts with the situation in individuals with injuries such as sunburn and other dermatological conditions where heat pain threshold drops substantially, for whom peripherally acting COX2 inhibitors may be more effective (62,63).…”

Preventive Analgesia and Novel Strategies for the Prevention of Chronic Post-Surgical Pain

“…The COX-2 isoform appears to be the enzyme responsible for inflammation and pain. COX-2 inhibitors, such asparecoxib, reduce secondary hyperalgesia and appear to reduce central sensitization in humans [38,39]. Celecoxib (the only COX-2 inhibitor approved in the North American marketplace) has demonstrated a reduction in postoperative pain, a reduced need for postoperative opioid analgesia [40], and did not inhibit bone healing following arthroplasty surgery [41].…”

The peripheral and central mechanisms of transition of acute to chronic pain and the possible role of cyclooxygenase-2 inhibition in the prevention of pain syndrome chronization

“…Однако как селективные, так и неселективные НПВП оказались неэффективными в отношении подавления сиг-нал-зависимой центральной сенситизации в исследованиях у здоровых добровольцев, вследствие чего был сделан вывод о том, что действие НПВП на этот механизм является опосредованным и реализуется через ингибирование пери-ферической сенситизации [21][22][23][24]. В то же время было про-ведено несколько фармакокинетических исследований, в которых на примере ряда НПВП, в основном коксибов, показана способность препаратов этой группы проникать через гематоэнцефалический барьер и накапливаться в цереброспинальной жидкости в концентрациях, теоретиче-ски достаточных для проявления свойственного им ЦОГ2-ингибирующего эффекта [25][26][27][28][29].…”