I am a
Home I AM A Search Login

Papers of the Week


Papers: 6 May 2023 - 12 May 2023

RESEARCH TYPE:
Basic Science


Animal Studies, Molecular/Cellular, Neurobiology

PAIN TYPE:
Abdominal/Pelvic Pain, Inflammation/Inflammatory


2023 May 11


J Neurochem


37165846

Peripheral and central neuroplasticity in a mouse model of endometriosis.

Authors

Castro J, Maddern J, Erickson A, Harrington AM, Brierley SM

Abstract

Chronic pelvic pain (CPP) is the most debilitating symptom of gynaecological disorders such as endometriosis. However, it remains unclear how sensory neurons from pelvic organs affected by endometriosis, such as the female reproductive tract, detect and transmit nociceptive events and how these signals are processed within the central nervous system (CNS) Using a previously characterised mouse model of endometriosis we investigated whether the increased pain sensitivity occurring in endometriosis could be attributed to i) changes in mechanosensory properties of sensory afferents innervating the reproductive tract, ii) alterations in sensory input from reproductive organs to the spinal cord, or iii) neuroinflammation and sensitisation of spinal neural circuits. Mechanosensitivity of vagina-innervating primary afferents was examined using an ex vivo single-unit extracellular recording preparation. Nociceptive signalling from the vagina to the spinal cord was quantified by phosphorylated MAP kinase ERK1/2 immunoreactivity. Immunohistochemistry was used to determine glial and neuronal circuit alterations within the spinal cord. We found that sensory afferents innervating the rostral, but not caudal portions of the mouse vagina, developed mechanical hypersensitivity in endometriosis. Nociceptive signalling from the vagina to the spinal cord was significantly enhanced in mice with endometriosis. Moreover, mice with endometriosis developed microgliosis, astrogliosis and enhanced substance P neurokinin-1 receptor immunoreactivity within the spinal cord, suggesting the development of neuroinflammation and sensitisation of spinal circuitry in endometriosis. These results demonstrate endometriosis-induced neuroplasticity occurring at both peripheral and central sites of sensory afferent pathways. These findings may help to explain the altered sensitivity to pain in endometriosis and provide a novel platform for targeted pain-relief treatments for this debilitating disorder.