Distribution and origin of corticotropin‐releasing factor‐immunoreactive axons in the female rat lumbosacral spinal cord

Abstract

Corticotropin-releasing factor (CRF) is a neuropeptide traditionally known for its hormonal role in the hypothalamic/pituitary/adrenal stress axis. However, CRF has been reported in axons in sites that may be considered outside of the direct stress axis, e.g., in axons in the lumbosacral spinal cord associated with the micturition response. Whether any of these CRF-immunoreactive axons interacts with uterine-related preganglionic autonomic neurons or projection neurons in the lumbosacral spinal cord is unknown. Thus, immunohistochemistry and retrograde tracing were employed to determine the presence, distribution, and origin of CRF-immunoreactive axons in the L6/S1 spinal cord of the female rat and to ascertain whether these axons are associated with uterine-related neurons. CRF-immunoreactive axons were present in the dorsal horn, medial and lateral collateral pathways, dorsal intermediate gray, laminae VlI and X, and sacral parasympathetic nucleus of the spinal cord. Nitric oxide-synthesizing, i.e., NADPH-d-positive neurons and pseudorabies virus labeled uterine-related neurons were in the sacral parasympathetic nucleus and were closely apposed by CRF-immunoreactive axons. Injection of retrograde tracers (fluorogold or fast blue) into the L6/S1 spinal cord labeled neurons in the hypothalamic paraventricular nucleus and pontine Barrington's nucleus, and some of these neurons were immunoreactive for CRF. This study demonstrates that CRF-immunoreactive axons are present in the L6/S1 spinal cord of the female rat in areas associated with sensory and autonomic processing. Some of these axons originate from the paraventricular nucleus and Barrington's nucleus and are adjacent to uterine-related neurons. These results indicate that CRF may influence neural activity related to the female reproductive system.

Expression of corticotropin-releasing factor and CRF receptors in micturition pathways after cyclophosphamide-induced cystitis

“…In contrast, CRF IR in the dorsal horn was still evident and may indicate that other sources (i.e., afferent cells in the DRG) contribute to the dorsal horn staining as well, or perhaps, exclusively (48). However, Puder and Pakpa (37) indicate that no CRF IR DRG cells have been identified. Thus CRF may add to the ever-growing list of similarities between urothelial cells and DRG cells.…”

“…CRF is expressed prominently in the descending pathway from Barrington's nucleus to the SPN in the lumbosacral spinal cord, and prominent CRF IR is expressed in the SPN of adult rats (37,53,54). Intrathecal administration of CRF decreases the amplitude of bladder contractions induced by electrical stimulation of Barrington's nucleus (34), suggesting that CRF in descending projections from Barrington's nucleus to the SPN is inhibitory.…”

“…Recent studies have led to the suggestion that Barrington's nucleus may contain neurons that control a broad range of pelvic organ functions (28,29,34,38,55). CRF is prominently expressed in the descending pathway from Barrington's nucleus to the SPN in the lumbosacral spinal cord, and prominent CRF immunoreactivity (IR) is expressed in the SPN of adult rats (37,53,54). Our recent studies have demonstrated an age-dependent upregulation of CRF IR in the SPN region and specifically in association with preganglionic parasympathetic neurons (48).…”

Chronic psychological stress enhances nociceptive processing in the urinary bladder in high-anxiety rats

“…A number of studies suggest that the CRF system might also be modulating visceral sensitivity related to stress [12,13,14,37]. With regard to the bladder, CRF is abundantly expressed in areas involved in the control of micturition (i.e., Barrington's nucleus, lumbosacral areas of the spinal cord) and administration of various CRF receptor agonists and antagonists alters cystometric parameters [38,39,40]. Following stress or bladder inflammation, increases in CRF-IR and/or CRF2 receptor expression have been detected in these areas and in the bladder itself [41,42].…”

Corticotropin-Releasing Hormone Reduces Pressure Pain Sensitivity in Humans without Involvement of β-Endorphin(1–31), but Does Not Reduce Heat Pain Sensitivity

“…Immunohistological studies indicate the presence of CRH in nerve fibers within the spinal dorsal horn [46], where the majority of pain-conducting, primary-afferent C fibers terminate. In terminals of the primary afferent C fibers, CRH is co-localized with substance P (SP) and excitatory amino acids, and both SP and excitatory amino acids are released upon noxious stimulation in the spinal cord dorsal horn [47].…”