Journal Article

Motor cortex and pain control: exploring the descending relay analgesic pathways and spinal nociceptive neurons in healthy conscious rats

Pagano, Rosana Lima, Campos, Ana Carolina Pinheiro, Britto, Luiz Roberto Giorgetti, Fonoff, Erich Talamoni, Lopes, Patrícia Sanae Souza

2019

Overview

Motor cortex stimulation (MCS) is an effective therapy for refractory neuropathic pain. MCS increases the nociceptive threshold in healthy rats via endogenous opioids, inhibiting thalamic nuclei and activating the periaqueductal gray. It remains unclear how the motor cortex induces top-down modulation of pain in the absence of persistent pain. Here, we investigated the main nuclei involved in the descending analgesic pathways and the spinal nociceptive neurons in rats that underwent one session of MCS and were evaluated with the paw pressure nociceptive test. The pattern of neuronal activation in the dorsal raphe nucleus (DRN), nucleus raphe magnus (NRM), locus coeruleus (LC), and dorsal horn of the spinal cord (DHSC) was assessed by immunoreactivity (IR) for Egr-1 (a marker of activated neuronal nuclei). IR for serotonin (5HT) in the DRN and NRM, tyrosine hydroxylase (TH) in the LC, and substance P (SP) and enkephalin (ENK) in the DHSC was also evaluated. MCS increased the nociceptive threshold of the animals; this increase was accompanied by activation of the NRM, while DRN activation was unchanged. However, cortical stimulation induced an increase in 5HT-IR in both serotonergic nuclei. MCS did not change the activation pattern or TH-IR in the LC, and it inhibited neuronal activation in the DHSC without altering SP or ENK-IR. Taken together, our results suggest that MCS induces the activation of serotonergic nuclei as well as the inhibition of spinal neurons, and such effects may contribute to the elevation of the nociceptive threshold in healthy rats. These results allow a better understanding of the circuitry involved in the antinociceptive top-down effect induced by MCS under basal conditions, reinforcing the role of primary motor cortex in pain control.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Analgesics / Analgesics - pharmacology / Animals / Antinociception / Behavioral Therapy / Biomedical and Life Sciences / Biomedicine / Brain / Cellular and molecular mechanisms / Cortex (motor) / Dorsal horn / Dorsal raphe nucleus / EGR-1 protein / Electrodes / Enkephalins / Eph protein / Hydroxylase / Hyperalgesia - metabolism / Immunoreactivity / Locus coeruleus / Male / Motor cortex / Motor Cortex - physiology / Motor task performance / Narcotics / Neuralgia / Neuralgia - therapy / Neurology / Neurons / Neurons - drug effects / Neurosciences / Neurostimulation / Nociceptors - drug effects / Opioids / Pain / Pain - physiopathology / Pain perception / Pain Threshold - drug effects / Periaqueductal Gray - metabolism / Periaqueductal gray area / Psychiatry / Raphe nuclei / Rats / Rats, Wistar / Rodents / Serotonin / Spinal cord / Spinal Cord - drug effects / Spine - drug effects / Substance P / Thalamic nuclei / Thalamus / Tyrosine 3-monooxygenase