OXTR rs53576 variation with breast and nipple pain in breastfeeding women

Abstract

Purpose: To evaluate associations among breast and nipple pain sensitivity and candidate pain sensitivity single-nucleotide polymorphisms [SNPs], (COMT rs6269, rs4633, rs4818, rs4680 and OXTR rs2254298, rs53576) in breastfeeding women. Design: A secondary analysis of sixty women participating in a pilot randomized controlled trial of a pain self-management intervention. Methods: All participants underwent standardized mechanical somatosensory testing for an assessment of pain sensitivity and provided baseline buccal swabs for genetic analysis. At 1, 2, and 6 weeks postpartum, women self-reported breast and nipple pain severity using a visual analogue scale. Results:- Women with the minor allele OXTR rs53576 reported 8.18-fold higher breast and nipple pain severity over time. For every 1-unit increase in mechanical detection threshold and windup ratio, women reported 16.51-fold and 4.82-fold higher breast and nipple pain severity respectively. Six women with the OXTR rs2254298 minor allele reported allodynia. Discussion: The presence of OXTR alleles in women with enhanced pain sensitivity suggests a phenotype of genetic risk for ongoing breast and nipple with potential for pain-associated breastfeeding cessation. Somatosensory testing identified women who reported higher breast and nipple pain during the first weeks of breastfeeding. Clinical Implications: Pain sensitivity testing can help to identify women at risk of intolerable and/or ongoing breastfeeding pain who may benefit from additional support to mitigate early breastfeeding cessation. Targeted interventions are needed to address breastfeeding pain, including management of infant latch, positioning, and infection as well as support for self-management of breastfeeding pain.

Neural Functions of Hypothalamic Oxytocin and its Regulation

“…Acute dental pain elevates salivary OT levels in pregnant women (Gurler et al, 2021). Women with the minor allele OTR rs53576 report 8.18-fold higher breast and nipple pain severity over time while women with the OTR rs2254298 minor allele also report allodynia (Lucas et al, 2021). This finding suggests that disorders in OT/OTR signaling can cause breast and nipple pain and its associated breastfeeding cessation.…”

Re-thinking lactation-related nipple pain and damage

“…Instead, this article proposes that the perception of nipple pain is triggered by acute tissue damage and inflammation, even when modulated by genetically moderated pain sensitivity, psychological state, and the impact of psychosocial factors. 91 It is important to note that although anxiety and depression modulate pain thresholds, anxiety and depression also result from the experience of pain with breastfeeding. 53…”

“…Instead, this article proposes that the perception of nipple pain is triggered by acute tissue damage and inflammation, even when modulated by genetically moderated pain sensitivity, psychological state, and the impact of psychosocial factors. 91 It is important to note that although anxiety and depression modulate pain thresholds, anxiety and depression also result from the experience of pain with breastfeeding. 53 The nipple dermis is dense with nociceptors; nipple stroma is richly vascularized and threaded with nerve fibres (Appendix 1); both are vulnerable to inflammation caused by mechanical stretching and deformational forces.…”