Colocalization of Oestrogen Receptor lmmunoreactivity and Preproenkephalin mRNA Expression to Neurons in the Superficial Laminae of the Spinal and Medullary Dorsal Horn of Rats

Abstract

A double-labelling procedure combining immunohistochemical staining with in situ hybridization using a radiolabelled cRNA probe was employed to demonstrate oestrogen receptor-like immunoreactivity and preproenkephalin-A mRNA in the medullary and spinal dorsal horn of female rats. Both markers labelled large numbers of neurons in the substantia gelatinosa and its trigeminal homologue. Many of these neurons were double-labelled, displaying both oestrogen receptor-like-immunoreactivity and preproenkephalin-A mRNA; cell counts showed that 40-60% of the of the oestrogen receptor-like-immunoreactive cells in the superficial laminae also were labelled for preproenkephalin-A mRNA, and that 60-70% of the preproenkephalin-A mRNA-labelled neurons in the same laminae displayed oestrogen receptor-like immunoreactivity. Previous studies have shown that oestrogen receptors can bind to the promoter region of the preproenkephalin-A gene, and studies on the hypothalamus have demonstrated that oestrogen regulates enkephalin expression in select neuronal populations. The present results demonstrate that enkephalinergic neurons in the superficial dorsal horn contain oestrogen receptors and suggest that oestrogen may play an important role in the modulation of sensory and nociceptive processing in the lower medulla and spinal cord.

Activation of Opioid Receptor Like-1 Receptor in the Spinal Cord Produces Sex-Specific Antinociception in the Rat: Estrogen Attenuates Antinociception in the Female, whereas Testosterone Is Required for the Expression of Antinociception in the Male

“…There are a number of possible molecular mechanisms via which estrogen might diminish OFQ-induced antinociception, including decreasing the expression of the ORL 1 receptor (Flores et al, 2003) and/or its coupling to G-proteins (for review, see Kelly and Wagner, 1999;Malyala et al, 2005), which would secondarily modify the affinity of OFQ to the ORL 1 receptor. Estrogen receptors (ER␣/ER␤) are present in spinal dorsal horn neurons (Amandusson et al, 1996(Amandusson et al, , 1999Shughrue et al, 1997), and estrogen, in addition to altering the expression of opioid peptides (Medina et al, 1993;Micevych et al, 1997;Amandusson et al, 1999;Micevych and Sinchak, 2001) (for review, see Craft et al, 2004), has also been shown by us and others to alter the expression of the ORL 1 receptor gene and protein in the trigeminal region and the hypothalamus (Sinchak et al, 1997;Flores et al, 2003;Sinchak et al, 2006).…”

Influence of Estrogen Levels on Thermal Perception, Pain Thresholds, and Pain Tolerance: Studies on Women Undergoing in Vitro Fertilization

“…[1][2][3][4]6,9,29 Nevertheless, the underlying networks are complex and the results of studies on hormonal pain modulation in humans, particularly those using laboratory induced pain, 14 remain notoriously diverse. 5,19,20,24,25,34,39,41 The clinical studies performed are generally based on a hormonal replacement therapy regimen.…”

“…This set-up thus offers the possibility to study pain perception in relation to extreme changes in estradiol levels in the same individual. 4 While responses to some pain stimuli have been examined during IVF treatment previously, 31,43 we here provide data from a comprehensive sensory testing protocol that examines different thin fiber modalities. We have employed a within-subject design to evaluate thresholds and tolerance to acute thermal pain, to pressure pain, and to tonic cold pain, at very low and very high serum levels of estradiol.…”

Pain sensitivity and cardiovascular reactivity to the experimental induced cold pressor pain during different phases of menstrual cycle in young Indian females

“…Few previous studies demonstrate less pain sensitivity during phases of the menstrual cycle associated with high estrogen which is reported by Hellstrom and Anderberg. [22] Amandusson et al reported that few estrogen receptor-expressing neurons are opioidergic [14] and show increased opioid transcription after taking estrogen. [23] One previous research study also reported the ovarian sex steroid antinociception as being mediated by opioid like mechanism and this might be due to activation of similar receptors in spinal cord.…”

“…[ [12][13][14] The female reproductive hormones have been reported to affect cardiovascular system in various ways, during the normal menstrual cycle. [15][16][17][18][19] The definitive interaction of these physiological characteristics is very meagerly found in literature search, particularly in young Indian females.…”