Pronociceptive changes in the activity of rostroventromedial medulla (RVM) pain modulatory cells in the streptozotocin-diabetic rat

• The spontaneous activity of RVM ON-like cells is increased in STZ-diabetic rat.
• The spontaneous activity of RVM OFF-like cells is decreased in STZ-diabetic rat.
• The STZ-diabetic rats present decreased numbers of active RVM OFF-like cells.
• Descending facilitation from the RVM concurs to diabetic neuropathic pain.
• Loss of descending pain inhibition from the RVM concurs to diabetic neuropathic pain.

Neuropathic pain is one of the most frequent complications of diabetes. The increased neuronal activity of primary afferents and spinal cord neurons in streptozotocin (STZ)-diabetic rats increases the recruitment of the nociceptive ascending pathways, which may affect the activity of pain control circuits in the brain. This study aimed to characterize the electrophysiological responses of neurons of the rostroventromedial medulla (RVM), a key brainstem area involved in descending modulation of nociceptive neurotransmission at the spinal cord, in STZ-diabetic rats. Spontaneous and noxious-evoked activity of ON-like cells (pain facilitatory cells) and OFF-like cells (pain inhibitory cells) in the RVM were analyzed by single cell extracellular electrophysiological recordings in STZ-diabetic rats with behavioral signs of diabetic neuropathic pain 4 weeks after diabetes induction and in age-matched non-diabetic controls (CTRL). The electrophysiological analysis revealed an increase in the spontaneous activity of RVM pronociceptive ON-like cells in STZ-diabetic rats when compared to CTRL. On the contrary, the number of active antinociceptive OFF-like cells was significantly lower in the STZ-diabetic rats and their spontaneous activity was decreased when compared with CTRL. Overall, the changes in the activity of RVM pain modulatory cells in STZ-diabetic rats point to enhancement of descending pain facilitation. Based on similar results obtained at the RVM in traumatic neuropathic pain models, the changes in the electrophysiological responses of RVM in STZ-diabetic rats may account for exacerbated pain-like behaviors in diabetic neuropathy.