GABAergic transmission and enhanced modulation by opioids and endocannabinoids in adult rat rostral ventromedial medulla

Key points Electrical stimulation of the rostral ventromedial medulla (RVM) facilitates pain behaviours in neonates but inhibits these behaviours in adults. The cellular mechanisms underlying these changes in RVM modulation of pain behaviours are not known. We optimized whole‐cell patch‐clamp recordings for RVM neurons in animals older than postnatal day 30 and compared the results to postnatal day 10–21 animals. Our results demonstrate that the γ‐aminobutyric acid (GABA) release is lower and opioid effects are more evident in adult rats compared to early postnatal rats. A cannabinoid receptor antagonist significantly increased GABA release in mature but not in immature RVM neurons suggesting the presence of local endocannabinoid tone in mature RVM. Neurons in the rostral ventromedial medulla (RVM) play critical and complex roles in pain modulation. Recent studies have shown that electrical stimulation of the RVM produces pain facilitation in young animals (postnatal (PN) day