The Influence of Early Life Experience on Visceral Pain

Abstract

Pain is the most reported and troublesome symptom of nearly all functional disorders affecting the genitourinary and gastrointestinal organs. Patients with irritable bowel syndrome (IBS), interstitial cystitis/painful bladder syndrome (IC/PBS), vulvodynia, and/or chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS; collectively termed chronic pelvic pain syndromes) report pain severe enough to impact quality of life and often suffer from symptoms of or are diagnosed with more than one of these syndromes. This increased comorbidity between chronic pelvic pain syndromes, and with pain disorders of disparate body regions, as well as with mood disorders, can be influenced by disruptions in the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the response to stress and influences the perception of pain. Experiencing trauma, neglect, or abuse in early life can permanently affect the functioning of the HPA axis. As such, a significant proportion of patients suffering from comorbid chronic pelvic pain syndromes report a history of early life stress or trauma. Here we will report on how these early life experiences influence chronic pelvic pain in patients. We will also discuss various rodent models that have been developed to study this phenomenon to understand the mechanisms underlying HPA axis dysfunction, as well as potential underlying mechanisms connecting these syndromes to one another.

Voluntary wheel running improves outcomes in an early life stress-induced model of urologic chronic pelvic pain syndrome in male mice

“…Early life stress exposure has been associated with the development of chronic pain and mood disorders later in life (3,(53)(54)(55)(56)(57). In patients with UCPPS, the severity of adverse childhood events is directly correlated with symptom severity and increased comorbidity, and is inversely related to likelihood of improvement (3,10).…”

Walking the Tightrope: A Proposed Model of Chronic Pain and Stress

“…These effects are primarily through feedback mechanisms controlling the HPA axis. Much of the previous research has focused on the effects of stress on the regulation of the HPA axis, although inconsistencies in the direction of the effect (Fuentes and Christianson, 2018) (hypoalgesic versus hyperalgesic) have made the extent and manner of impact on chronic pain unclear. Chronic pain patients have been shown to exhibit faulty adaption stress responses, including both normal experiences and in response to pain (Vachon-Presseau, 2018).…”

Pain in Endometriosis

“…It has been proposed that chronic sensitization of peripheral sensory nerve fibers in turn induces sensitization of the CNS in endometriosis ( Berkley et al, 2005 ; Arnold et al, 2012 ). Recent studies also show exposure to chronic stress early in life can increase the likelihood of CPP later in life, whilst bouts of acute stress can trigger or worsen symptoms ( Pierce et al, 2014 , 2015 ; Pierce and Christianson, 2015 ; Fuentes and Christianson, 2018 ).…”

“…Central sensitization can evoke long-term changes in pain processing, similar to the generation of ‘memory.’ Neonatal irritation of hollow organs or maternal separation are able to drive long-term visceral/somatic hypersensitivity and central sensitization ( Pierce et al, 2014 , 2015 ; Fuentes and Christianson, 2018 ). Central sensitization is also often initiated and maintained by peripheral sensitization, resulting in pain persisting long after the peripheral insult or pathology or has resolved ( Table 2 ) ( Woolf, 2011 ).…”