Naloxone does not alter the perception of pain induced by electrical and thermal stimulation of the skin in healthy humans

Abstract

It has been hypothesized that, in the absence of acute or chronic pain, a tonically active system exists involving opioid peptides, which ensures a certain level of pain insensitivity. Although various studies have failed to support this concept, it has been reported that in conditions of both experimentally induced and clinical pain, high doses of the opioid antagonist naloxone induced a state of hyperalgesia and thus seemed to set off this hypothetical system. Lower doses were, however, without effect or even acted as analgesics. This study investigated the effect of 5 and 20 mg naloxone i.v., compared to placebo, on the perception of pain in healthy humans. Pain was induced by two methods, using electrical and thermal stimulation of the skin, which have previously been shown to be sensitive to the effects of opioid as well as of non-steroidal anti-inflammatory analgesics. Each of 12 males and 12 females participated in 3 experimental sessions, in which the treatments were administered double-blind according to a Latin square design. Threshold and tolerance to electrically induced pain and threshold to thermally induced pain were measured at 30 min intervals for 90 min before and 90 min after drug administration. Electrical stimuli were square wave constant current impulses of linearly increasing intensity; thermal stimuli were of constant intensity and variable duration. Threshold and tolerance to electrically induced pain were not altered by either dose of naloxone, whereas the threshold to thermally induced pain was significantly higher after both 5 and 20 mg naloxone than after placebo, the effects of the two naloxone doses not differing from each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Negative affect, pain and sex: The role of endogenous opioids

“…The effects of µ-opioid receptor blockade on experimental pain are inconsistent, with reports of pain increasing after naloxone administration (Buchsbaum et al, 1983;Borras et al, 2004), not changing (El-Sobky et al, 1976;Grevert and Goldstein, 1978), or decreasing (Stacher et al, 1988;Al'Absi et al, 2004). This inconsistency may be due to individual differences in pain sensitivity (Buchsbaum et al, 1983) or could be dose-related.…”

FMRI Measurement of CNS Responses to Naloxone Infusion and Subsequent Mild Noxious Thermal Stimuli in Healthy Volunteers

“…Some studies report that naloxone increased pain after noxious stimuli (Buchsbaum et al 1983), whereas others suggest that there is no alteration in pain threshold but an increase in pain-associated anxiety (Grevert andGoldstein 1977, 1978;Stacher et al 1988). Naloxone administration also has effects on clinical pain: it both enhances baseline clinical pain and diminishes the analgesic effectiveness of a placebo (Grevert et al 1983).…”

Nociceptive flexion reflex and pain rating responses during endogenous opiate blockade with naltrexone in healthy young adults

“…Early studies by Buchsbaum and colleagues demonstrated naloxone-related hyperalgesia (Buchsbaum et al 1977;Davis et al 1978;Buchsbaum et al 1983), although these effects were limited to specific individuals (e.g., "pain insensitive" participants) or conditions (e.g., prolonged or intense stimulation). Other studies have reported that naloxone has no effect on forearm ischemic pain (Grevert and Goldstein 1977;Grevert et al 1983a;Grevert et al 1983b;Posner and Burke 1985), cold pressor pain (Grevert and Goldstein 1978;McCubbin and Bruehl 1994), or electrocutaneous pain in response to stimulation applied to the finger (Bromm et al 1983), forearm (El-Sobky et al 1976), ear (Stacher et al 1988), or teeth (Ernst et al 1986). Finally, a few studies have suggested that, in some cases, opioid antagonists may actually inhibit pain (Volavka et al 1979;Tassorelli et al 1995;Janssen and Arntz 1997).…”