Normal distribution of alpha 2‐adrenoceptors in the rat spinal cord and its modification after noradrenergic denervation: A quantitative autoradiographic study

Abstract

The distribution of alpha 2 (alpha 2)-adrenoceptors along cervical, thoracic, lumbar, and sacral segments of the spinal cord of normal rats has been studied by quantitative autoradiography using the specific alpha 2-antagonist [3H]rauwolscine as a ligand. In addition, the influence of noradrenergic (NA) denervation [obtained either by complete transection of the spinal cord at vertebrae level T8-T9 or by selective lesion of NA spinal cord system carried out by intracisternal injection of 6-hydroxydopamine (6-OHDA)] on eventual variations of alpha 2-adrenoceptor density at spinal cord target cells was studied in parallel. In control rats, the quantitative analysis of alpha 2-adrenoceptor densities revealed the presence of these receptors throughout the whole gray matter with a preferential location in the superficial dorsal horn. This pattern was the same at all rostro-caudal levels of the cord and appeared very well correlated with the distribution of NA terminals revealed by immunohistochemistry, particularly in the superficial layers of the dorsal horn. After total transection of the spinal cord (caudally to the section) and 6-OHDA-induced lesion, an increase of alpha 2-adrenoceptor density was mainly observed within the distal dorsal horn thus evidencing supersensitivity in this area, while modifications were not detectable in other regions of the spinal gray matter, except at the lumbar level where other dorsal, central, and intermediate zones were significantly enriched.

Adrenergic Receptors Modulate Motoneuron Excitability, Sensory Synaptic Transmission and Muscle Spasms After Chronic Spinal Cord Injury

“…There are consistent reports of small amounts of residual NA that persists in the spinal cord after SCI (Magnusson 1973;Roudet et al 1993Roudet et al , 1994, although the origin of this NA remains a matter of dispute. Based on biochemical methods to visualize catecholamines in the spinal cord, McNicholas et al (1980) suggested that this residual NA after SCI arises from small sympathetic efferents branching off of blood vessels in the spinal cord.…”

“…Indeed, previous studies have shown that ␣ 2 receptors on motoneurons induce a hyperpolarization by blocking I h currents (Adachi et al 2005;Parkis and Berger 1997;Rekling et al 2000), and such I h currents contribute ϩ10 mV to the resting potential in our chronic spinal rats ). Furthermore, ␣ 2 receptor expression can be detected throughout the spinal cord with the highest densities in the superficial dorsal horn and moderate densities in the portion of be ventral horn containing motoneurons (Giroux et al 1999;Roudet et al 1994). All together, ␣ 2 receptor agonists like clonidine or tizanidine are likely to produce their antispastic action primarily by inhibiting afferent transmission to motoneurons and secondarily by hyperpolarizing motoneurons, making motoneurons less likely to be activated during a muscle spasm.…”

Effects of Localized Intraspinal Injections of a Noradrenergic Blocker on Locomotion of High Decerebrate Cats

“…However, preliminary unpublished data in spinal cats indicate that 30 days following spinalization, alpha2-noradrenergic receptors are upregulated in segments L3-L5 (lamina II, III, V, and X) and down-regulated from L6 or L7 to S3 segments (lamina II, III, V, VI, VII, and X), suggesting the importance of these receptors in midlumbar segments in the expression of spinal locomotion (Chau et al 2000). In intact rats, alpha2-noradrenergic receptors were correlated with the distribution of NA terminals and were found at all rostrocaudal levels of the spinal cord throughout the whole gray matter with a preferential location in the superficial dorsal horn (Roudet et al 1994). …”

Increased Presynaptic and Postsynaptic α2-Adrenoceptor Activity in the Spinal Dorsal Horn in Painful Diabetic Neuropathy

“…At the spinal level, the ␣ 2 -adrenoceptor is present presynaptically at the primary afferent terminals and postsynaptically on dorsal horn neurons. Although the ␣ 2A -adrenoceptor subtype is located predominantly on the terminals of primary afferents (Sullivan et al, 1987;Roudet et al, 1994;Stone et al, 1998;Overland et al, 2009;Riedl et al, 2009), the ␣ 2C -adrenoceptor subtype is present mainly on spinal dorsal horn neurons (Stone et al, 1998). Stimulation of ␣ 2 -adrenoceptors with clonidine dose-depend-ently reduces excitation of dorsal horn neurons evoked by primary afferent stimulation (Sullivan et al, 1987).…”