Pleasure-related analgesia activates opioid-insensitive circuits

Abstract

Recent findings suggest that pain and pleasure share common neurochemical circuits, and studies in animals and humans show that opioid-mediated descending pathways can inhibit or facilitate pain. We explored the role of endogenous opioid neurotransmission in pleasure-related analgesia. μ-Opioidergic activity was blocked with 0.2 mg/kg naloxone to assess its effects on hedonic responses to pleasant emotional pictures (International Affective Picture System) and its modulating effects on heat pain tolerance. Naloxone did not alter subjective and autonomous reactions to pleasure induction or overall mood of participants. In addition, pleasure-related increases in pain tolerance persisted after reversal of endogenous μ-opioidergic neurotransmission. Subjective pain intensity and unpleasantness ratings increased after naloxone administration. These findings suggest that, in addition to opioid-sensitive circuits, mainly opioid-insensitive pain-modulating circuits are activated during pleasure-related analgesia.

Figure 1.

Schematic depiction of an experimental session consisting of two blocks. Each block (∼13 min in length) included pain-tolerance measurements before and after a period of picture viewing consisting of 15 pleasant IAPS pictures (180 s in total). Pain-tolerance measurements were followed by subjective pain ratings. At the end of each block, subjective ratings on emotional state during picture viewing were collected. In between blocks, drug was administered, followed by a 3 min distraction task. Red bars represent the use of noxious heat stimuli and their associated pain-tolerance measurement. Vertical arrows represent scales and questionnaires displayed on a computer screen. Autonomic reactivity was measured during picture viewing periods in which three acoustic startle stimuli were presented (grouped vertical arrows).

Figure 2.

Mean levels of heat pain tolerance (°C) before (pre) and after (post) picture viewing in block 1 (before drug administration) and block 2 (after drug administration). Pain tolerance increased significantly after picture viewing in both blocks but decreased after drug administration only. Asterisks indicate significant, post hoc comparisons (p < 0.05). Bars depict average values and SEs.

Figure 3.

A, B, Mean VAS pain-intensity ratings (A) and mean VAS pain-unpleasantness ratings (B) in block 1 (before drug administration) and block 2 (after drug administration). VAS ratings increased in block 2 significantly but only in the naloxone group. Asterisks indicate significant, post hoc comparisons (p < 0.05). Bars depict average values and SEs.