Does central sensitization help explain idiopathic overactive bladder?

Abstract

The pathophysiological mechanisms underlying overactive bladder syndrome (OAB) can include dysfunction of sensory pathways of the peripheral and central nervous systems, resulting in bladder hypersensitivity. Central sensitization describes an induced state of spinal hypersensitivity that is associated with a variety of chronic pain disorders that share many attributes with OAB, albeit without the presence of pain. As such, the concept of central sensitization might be relevant to understanding the mechanisms and clinical manifestations of OAB syndrome. An understanding of the pathophysiology and clinical manifestations of central sensitization, and the evidence that supports a role of central sensitization in OAB, including the potential implications of mechanisms of central sensitization for the treatment of patients with OAB could provide a novel approach to the treatment of patients with this disease. Such an approach would be especially relevant to those patients with central sensitization-related comorbidities, and has the potential to improve the outcomes of these patients in particular.

Figures

Figure 1. Mechanisms of central sensitization

a ∣ Normal sensation. The somatosensory system is organized in separate, parallel pathways, such that low-intensity stimuli only activate the central pathways that lead to innocuous sensations such as touch, whereas high-intensity stimuli that activate nociceptors only activate the central pathways that lead to pain. This effect is mediated by the strong synaptic inputs between the particular sensory pathways and by inhibitory neurons that focus activity to these dedicated circuits. b ∣ Central sensitization. With the induction of central sensitization, the pain response to noxious stimuli is enhanced (hyperalgesia), whereas the sensitivity of the normally ineffective convergent synapses is strengthened, allowing low-threshold sensory inputs to activate the pain circuit (allodynia). Reproduced with permission obtained from Lippincott Williams & Wilkins © Woolf, C. J. Pain152, S2–S15 (2011).

Figure 2. Temporal summation

During quantitative sensory testing, the perception of pain intensity assessed with a visual analogue scale (VAS) in response to a repetitive thermal stimulation of uniform intensity applied to the forearm will gradually increase owing to central sensitization. In a patient with chronic pain, central sensitization facilitates temporal summation, whereas, in a healthy person, this intensity does not increase owing to habituation to the stimulus. Modified with permission obtained from Springer © Arendt–Nielsen, L. Handb. Exp. Pharmacol.227, 79–102 (2015).

Figure 3. Hypothetical roles of central sensitization in overactive bladder (OAB)

Persistent activation of peripheral nociceptive C-fibres, such as those that project from the bladder or related pelvic organs (such as the colon), could induce central sensitization in second-order spinal neurons. Once established, central sensitization might contribute to overactive bladder by (1) facilitating ascending transmission of normally low-threshold mechanoreceptor signals from bladder afferents (afferent noise) or (2) from other pelvic organs via crosstalk with afferent signalling pathways that project from other organs. In addition (3), descending neural projections might also facilitate afferent spinal transmission of bladder signals in the setting of central sensitization. Modified with permission obtained from Nature Publishing Group © Thakur, M. et al. Osteoarthritis pain: nociceptive or neuropathic? Nature Reviews Rheumatology10, 374–380 (2014).