Participation of μ‐opioid, GABA_B, and NK1 receptors of major pain control medullary areas in pathways targeting the rat spinal cord: Implications for descending modulation of nociceptive transmission

Abstract

Several brain areas modulate pain transmission through direct projections to the spinal cord. The descending modulation is exerted by neurotransmitters acting both at spinally projecting neurons and at interneurons that target the projection neurons. We analyzed the expression of mu-opioid (MOR), gamma-aminobutyric acid GABA(B), and NK1 receptors in spinally projecting neurons of major medullary pain control areas of the rat: rostroventromedial medulla (RVM), dorsal reticular nucleus (DRt), nucleus of the solitary tract, ventral reticular nucleus, and lateralmost part of the caudal ventrolateral medulla. The retrograde tracer cholera toxin subunit B (CTb) was injected into the spinal dorsal horn, and medullary sections were processed by double immunocytochemistry for CTb and each receptor. The RVM contained the majority of double-labeled neurons followed by the DRt. In general, high percentages of MOR- and NK1-expressing neurons were retrogradely labeled, whereas GABA(B) receptors were mainly expressed in neurons that were not labeled from the cord. The results suggest that MOR and NK1 receptors play an important role in direct and indirect control of descending modulation. The co-localization of MOR and GABA(B) in DRt neurons also demonstrated by the present study suggests that the pronociceptive effects of this nucleus may be controlled by local opoidergic and GABAergic inhibition of the pronociception increased during chronic pain.

Substance P Enhances Excitatory Synaptic Transmission on Spinally Projecting Neurons in the Rostral Ventromedial Medulla After Inflammatory Injury

“…Although previous extracellular unit recordings determined that SP excites a subset of RVM neurons (Budai et al 2007;Pomeroy and Behbehani 1980), these studies provided little information as to their projections and neurotransmitter content. A recent study in adult rat also determined that a majority of spinally projecting neurons express NK1 receptor immunoreactivity but did not determine the neurotransmitter content of those neurons (Pinto et al 2008). Neither whole cell recordings nor an immunohistochemical analysis identified NK1 receptors on serotonergic RVM neurons.…”

Interferon-Alpha Enhances Excitatory Transmission in Substantia Gelatinosa Neurons of Rat Spinal Cord

“…morphine), which mainly target MORs, remain the most powerful analgesics available for pain relief [14,15,16,17,18,19]. Previous studies showed that MORs and β-endorphin-sensitive opioid receptors have been expressed in the dorsal root ganglia neurons and the superficial dorsal horn of the spinal cord [20,21,22]. Many experiments have proven that opioid receptors are involved in the modulation of nociceptive afferent transmission and opioid analgesia at the spinal cord [18,19,23].…”

Differential modulation of neurons in the rostral ventromedial medulla by neurokinin-1 receptors

“…SP and NK-1 receptors have been identified in the RVM (Budai et al 2007;Marson and Loewy 1985;Saffroy et al 1988Saffroy et al , 2003, and nearly half of the NK-1-expressing neurons from RVM project to the dorsal horn of the spinal cord (Pinto et al 2008). Dickenson and colleagues originally proposed a pathway through which excitation of NK-1-expressing neurons in the superficial spinal dorsal horn leads to descending facilitation (Suzuki et al 2002) via serotonin and 5-HT 3 receptors in the spinal cord (Suzuki et al 2004a(Suzuki et al , 2004b; see also Lagraize et al 2010).…”