Naloxone increases pain induced by topical capsaicin in healthy human volunteers

Abstract

Opioid receptors occur in locations of strategic importance within the central nervous system for modulation of pain. Is pain reduced by ongoing inhibition mediated by activation of these receptors? Experiments to date in which the opioid-receptor antagonist, naloxone, is administered during a painful event have yielded unclear results. Topically applied capsaicin can be used to induce tonic pain of moderate to severe intensity without tissue injury and is an ideal stimulus for studying acute pain modulation. We therefore conducted a placebo-controlled double-blind crossover study to investigate the effects of naloxone on capsaicin-induced pain (five men, four women, aged 29 +/- 5 years). Capsaicin (10%) was applied topically and subjects rated pain every 2 min. The subjects were told that any drug given to them could increase, decrease, or not change their pain sensation. Pain plateaued after 20 min. At 26 min subjects received either naloxone or placebo in double-blind fashion. At 56 min subjects received the alternative (placebo or naloxone). In a second session the order of presentation was reversed. The naloxone induced a significant increase in pain compared both to baseline (P < 0.01) and placebo (P < 0.01). The peak effect, reached at 12-20 min after naloxone delivery, was 59% greater than placebo. This experiment suggests that acute pain is actively suppressed by endogenous opioid-receptor activation.

Windup in Dorsal Horn Neurons Is Modulated by Endogenous Spinal μ-Opioid Mechanisms

“…The finding that the encoding of acute noxious and nonnoxious mechanical stimuli by deep WDR neurons is not altered in MOR Ϫ/Ϫ mice is in line with previous behavioral observations: MOR Ϫ/Ϫ mice showed normal pain behavior to acute noxious stimuli (Fuchs et al, 1999;Mansikka et al, 2004). However, psychophysical studies and animal pharmacological experiments yield conflicting results on the effect of naloxone on acute pain perception (El-Sobky et al, 1976;Buchsbaum et al, 1977;Anderson et al, 2002). The group effect of naloxone on the response of WDR neurons to graded electrical stimulation was not significant.…”

Pharmacological dissection of the paradoxical pain induced by a thermal grill

“…It is unlikely that these "negative" results were due to an insufficient dose, because in previous studies similar or lower doses of naloxone modulated complex responses related to pain perception such as the placebo effect or the experimental pain induced by capsaicin (e.g. Levine et al, 1979;Gracely et al,, 1983;Anderson et al, 2002). However, our study does not rule out the involvement of endogenous opioids in this phenomenon.…”

“…The doses of ketamine and naloxone were chosen on the basis of the numerous previous studies using these drugs in various experimental and clinical pain models (e.g. Buchsbaum et al, 1977;Levine et al, 1979;Grevert et al, 1983;Guirimand et al, 2000;Brennum et al, 2001;Anderson et al, 2002, Bossard et al, 2002Strigo et al, 2005).…”

Capsaicin-induced thermal hyperalgesia and sensitization in the human trigeminal nociceptive pathway: An fMRI study

“…DLPFC encodes cognitive control of complex actions (Fuster, 2001;Koechlin et al, 2003;MacDonald et al, 2000), and may affect pain perception through cortico-subcortical and cortico-cortical modulatory mechanisms (Apkarian et al, 2004;Lorenz et al, 2003;Maihofner and Handwerker, 2005;Wager et al, 2004;Zubieta et al, 2005). DLPFC is commonly active in pain imaging studies, and may participate in a proposed pain-induced analgesia circuit (Anderson et al, 2002;Bencherif et al, 2002;Gear et al, 1999;Zubieta et al, 2001). This suggests that DLPFC changes during capsaicin-induced sensitization reflect an increase in its capacity to modulate nociceptive processes.…”