Specific innervation of aromatase neurons by substance P fibers in the dorsal horn of the spinal cord in quail

Abstract

The enzyme aromatase catalyzes the production of estrogens in the dorsal horn of the spinal cord where most of the nociceptive primary afferent fibers terminate. Numerous estrogen receptors are present in this area and the control of spinal aromatase activity is thought to play an important role in the estrogenic control of nociception. The coexistence of aromatase and nociceptive terminals suggests a role for aromatase cells in pain-related processes, but whether terminals releasing nociceptive neuropeptides (e.g., substance P) actually contact aromatase neurons is unknown and the factors that control spinal aromatase activity have not yet been identified. In the present study we analyzed by double-label immunocytochemistry the distribution in the Japanese quail spinal cord, of aromatase and of substance P or its receptor (neurokinin 1 receptor). All antigens were mainly localized in laminae I and II as observed in mammals. Most aromatase neurons were colocalized with neurokinin 1 receptors and were in close apposition with substance P-immunoreactive fibers. These results suggest that aromatase neurons are responsive to noxious stimulation and may participate in the control of nociception. Furthermore, spinal aromatase activity could be controlled by substance P through a regulation of the aromatase gene transcription as reported for the mouse diencephalon and/or through neurokinin 1 receptor-dependent phosphorylation of the aromatase protein.

Importance of sex to pain and its amelioration; relevance of spinal estrogens and its membrane receptors

“…Either of two structurally dissimilar inhibitors of aromatase, vorozole or 1,4,6-androstatriene-3,17-dione, increases foot withdrawal latency within one min following their intrathecal application [64]. Additionally, primary afferent transmitters such as glutamate (via NMDA or kainate receptor subtypes) or substance P, both of which are released in response to nociceptive stimuli, can reversibly depress aromatase activity [13,14,66]. Importantly, aromatase neurons in the spinal cord colocalize with neurokinin 1 receptors and are in close apposition with substance P-immunoreactive fibers suggesting a physiological role for interactions between afferent transmitters and spinal cord aromatase.…”

Is it All about Sex? Acupuncture for the Treatment of Pain from a Biological and Gender Perspective

“…The oestrogen-producing enzyme aromatase is present in the dorsal horn of the spinal cord, 48 where peripheral nociceptive neurons terminate and pain signals are modulated. Aromatase activity was recently found to be involved in the establishment of thermal nociceptive threshold.…”

“…Aromatase activity was recently found to be involved in the establishment of thermal nociceptive threshold. 48 Having the oestrogen-producing enzyme and the ERs adjacent to each other opens the possibility that concentration changes occur rapidly and only on a very local level, which therefore might not be reflected in changes of the more constant plasma levels. Indeed, a local rise in oestrogen by injection into the rat hindpaw results in decrease of mechanical hyperalgesia induced by intracellular signalling molecules.…”

Estrogens as arbiters of sex-specific and reproductive cycle-dependent opioid analgesic mechanisms

“…The ovaries are the predominant source of estrogens. However, we now know that throughout the central nervous system (CNS) there is expression of aromatase (Balthazart, Baillien, & Ball, 2001, 2006Evrard, 2006;Evrard et al, 2000;Evrard, Willems, Harada, & Balthazart, 2003;Jakab, Harada, & Naftolin, 1994;Liu, Chakrabarti, Schnell, Wessendorf, & Gintzler, 2011;Liu, Murugaiyan, Storman, Schnell, Wessendorf, et al, 2017b) (a key enzyme in the synthesis of estrogens), along with multiple types of estrogen receptor (ER) (Hazell et al, 2009;Merchenthaler, Lane, Numan, & Dellovade, 2004;Mitra et al, 2003;Perez, Chen, & Mufson, 2003;Shughrue & Merchenthaler, 2001). This resulted in a profound change in the functional categories used to describe estrogenic actions, i.e., not exclusively as hormones, but also as neuroactive agents that are intrinsic to the CNS.…”