A large clinical trial revealed sex differences in how endogenous opioids mediated pain relief during meditation, with potential implications for developing sex-specific pain treatments.
In one of the largest meditation-focused intravenous naloxone crossover trials to date, published in PNAS Nexus, researchers found that opioid receptor blockade reversed meditation-induced analgesia in male patients but not in female patients. The study combined data from two randomized clinical trials involving 98 participants (51 female patients and 47 male patients), including both healthy individuals and those with chronic low back pain.
The study employed a double-blind, counterbalanced design using high-dose naloxone (15 mg/kg bolus + 0.1 mg/kg/hour) vs placebo saline. The participants underwent either mindfulness meditation or sham mindfulness training prior to experiencing noxious heat stimulation (49°C) to the calf.
Male patients showed pain reduction during meditation with saline infusion, but this effect was abolished with naloxone administration. Female patients maintained pain relief during meditation even when opioid receptors were blocked. Additionally, meditation-induced analgesia was greater in the patients with chronic low back pain compared to healthy volunteers.
"These findings demonstrated that self-regulated analgesia in males, but not in females, was opioidergically mediated," the study authors suggested. They noted that this aligned with preclinical rodent studies showing sex-specific differences in opioid-mediated pain modulation.
The researchers indicated that sex-based differences in endogenous analgesic systems might be associated with distinct evolutionary-based mechanisms supporting pain relief. They speculated that other systems such as the endocannabinoid system might play a larger role in female analgesia.
The opioid-mediated effect in male patients was observed across both healthy adults and those with chronic pain, indicating a generalized between-sex effect regardless of pain status. The researchers found that the patients with chronic pain produced greater meditation-induced analgesia (–18%) compared with pain-free individuals (–3%).
The researchers noted that these results highlighted the need for establishing and promoting sex-specific pain therapeutics. They also reported that extensive mental training was not required to elicit pain reduction, potentially removing a barrier to translating mind-body approaches for chronic pain treatment.
Study limitations included the lack of measurement of endocannabinoid concentrations, menstrual cycle, and gonadal hormone levels, which are known to play a role in sex-based pain differences.
The authors declared having no competing interests.