Pain neuroscience in the female athlete

Females go through puberty and develop primary and secondary sexual characteristics resulting from an upregulation in key hormonal levels. Canonical fluctuations in hormones including oestrogen and progesterone are initiated in the brain via hypothalamic pathways and have established relationships with pain sensitivity at the neuronal level 4 that can result in either sensitisation or attenuation of nociceptive signals. Engaging in exercise may mediate pain symptoms; however, physical activity withdrawal occurs more for girls than for boys during puberty, 5 making them more prone to pain conditions. In menopausal females, ovarian oestrogen and progesterone levels decline, which have a downstream impact on hypothalamic function. During pregnancy, oestrogen and progesterone are conversely upregulated and required to support fetal development alongside optimal hypothalamic functioning. Notably, research into both menopause and pregnancy in athletic and non-athletic populations is very limited; thus, known variations in hormonal levels have not been explored for their impact on pain neuroscience. Clinically, adolescence and the onset of menarche are associated with a rise in sex-specific conditions, such as endometriosis and dysmenorrhoea, which can involve debilitating levels of pain (Harada, 2013). A recent review of Olympic level athletes showed a significant increase in reporting of dysmenorrhoea over a 12-year Olympic lifespan. 6 No research to date has evaluated brain neuroimaging in dedicated athlete cohorts with gynaecological pain; however, non-athletic populations have shown changes in brain structure, 7 highlighting the need to study pelvic health more holistically including how it influences and is influenced by the brain. From the point of puberty onwards, the prevalence of pain reporting in females has significantly increased relative to that in males across clinical conditions, suggesting that underlying sex-based (eg, hormonal) factors as well as societal and gendered environmental factors may mediate this process. 5 Notably, under-reporting of female pelvic pain conditions, particularly in athletic cohorts, 8 will contribute to a higher incidence and prevalence than is currently understood.

Pain modulation underscores the notion that nociception does not always have a linear relationship with pain perception. It also invites the notion that internal (eg, neuronal) and external (eg, sociocultural) environmental factors can influence this relationship and make persons more or less prone to experience an event as painful. Female athletes arguably face a unique set of stressors that influence pain perception. For example, relative energy deficiency in sport (RED–S), a condition that has a higher prevalence in female athletes, reflects a chronic and/or severe low energy availability from a mismatch in energy demands and nutritional intake, which can lead to heightened pain perception. 9 – 11 Persons with RED-S can experience menstrual dysfunction, stemming from impaired hormonal signalling at the hypothalamus (hypothalamic gonadotropin-releasing hormone (GnRH) pulsatility) as well as an impaired neuroendocrine response to stress. 12 Heterogeneity in health and pain across the menstrual cycle represents a significant clinical challenge in female healthcare, and fluctuations and/or disruptions in hormonal levels may represent a risk factor for pain sensitivity. Considering that the hypothalamus, in particular the periventricular nucleus, has been implicated in regulating visceral pain, 13 we need to be cognisant of how stressors can aggregate to manipulate pain vulnerability at the neuronal level. A strong path forward will be to develop complex biopsychosocial perspectives that integrate pain neuroscience to support female athlete health.

With growing attention being paid to the health and well-being of female athletes, there is an opportunity to integrate a neuroscience perspective and, with it, a better understanding of the factors leading to pain perception. First, we need to better recognise and integrate pain reporting in female athletes using methods that athletes feel comfortable engaging with. We need better ways for athletes to bring forward information, as prior work suggests as much as 78% of female athletes experience pelvic floor symptoms and do not disclose symptoms (78.2%) or seek specialised care (95.1%). 8 Second, we need to improve pain neuroscience education. A lack of pain reporting is only half of the narrative. Active (eg, attention modulation) and passive (eg, descending/ascending) forms of pain modulation can have female-specific considerations and divorce nociceptive stimulation from active pain perception. As summarised in figure 1 , through greater study of visceral pain disorders, hormonal interactions with pain receptors, and brain health in acute/chronic pain, we can achieve a better understanding of nociception and pain-related factors that limit athletic performance in female athletes.

The central nervous system (CNS) is critical in translating nociception to pain perception. Primary afferent neurons are responsible for the detection of nociceptive stimuli and send afferent projections through interneurons and the spinal cord to subcortical structures, which then project throughout the cortex. However, nociception does not always lead to perceived pain. Pain represents ‘an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage’. 2 Even when tissue pathology occurs, sensitisation or pain modulation efforts can mediate this relationship. Brain regions such as the periaqueductal grey, prefrontal cortex and anterior cingulate cortex can be involved in a process called descending pain modulation, where descending efferent fibres modulate the extent to which a nociceptive stimulus is translated into active pain perception. Failure in mechanisms such as descending pain modulation has been implicated in some forms of pelvic pain including endometriosis and other gynaecological conditions, 3 suggesting a link between CNS function and female pelvic pain.