The effect of repeated intramuscular alfentanil injections on experimental pain and abuse liability indices in healthy males

Abstract

Objective: Opioid-induced hyperalgesia (OIH), increased sensitivity to noxious stimuli after repeated opioid exposures, has been demonstrated in preclinical studies. However, there is no accepted, prospective model of OIH after repeated opioid exposures currently available in humans. This study assessed a potential prospective OIH model.

Methods: Double-blind intramuscular injections of a short-acting opioid (alfentanil 15 mcg/kg; N=8) were compared to active placebo (diphenhydramine 25 mg; N=3) on cold and pressure pain testing and standard abuse liability measures in eight 10-hour sessions (1 injection/session) over 4 to 5 weeks in healthy, pain-free males. Decreases from session baseline pain threshold (PThr) and tolerance (PTol) were calculated to represent hyperalgesia, and were assessed both within and across sessions.

Results: Mean decreases in cold PTol were seen in the alfentanil group at 180 minutes (-3.8 s, ±26.5) and 480 minutes (-1.63 s, ±31.5) after drug administration. There was a trend for differences between conditions on cold PThr hyperalgesia but not for pressure PThr. Alfentanil participants had greater mean ratings on Liking and High visual analog scales at peak effects (30 min), but these scores did not change across sessions.

Discussion: Repeated alfentanil exposures over 4 to 5 weeks resulted in within session decreases in cold pain tolerance from baseline but these differences were not substantially different from diphenhydramine controls. The results did not support the phenomenon of OIH in this model, although definitive conclusions regarding the existence of OIH in humans likely requires a larger sample size or an alternative model.

Conflict of interest statement

DISCLOSURES

The authors have no conflicts of interest relevant to this manuscript to disclose. Preliminary analyses in this manuscript were presented at the 2010 American Pain Society and 2011 College on Problems of Drug Dependence annual meetings.

Figures

Figure 1

CONSORT diagram of eligible participants. CPT=cold pressor test.

Figure 2

Mean change from baseline cold pain tolerance (CFBL cold PTol) within session.

Figure 3

Mean change from baseline cold pain tolerance (CFBL cold PTol) across sessions.

Figure 4

Mean baseline (BL) measure of cold pain tolerance (cold PTol) across sessions.

Figure 5

Aggregate ratings of abuse liability measures at peak drug effects (30 minutes after injection).