Neurobiological mechanisms of pelvic pain

Massimo Origoni, Umberto Leone Roberti Maggiore, Stefano Salvatore, Massimo Candiani, Massimo Origoni, Umberto Leone Roberti Maggiore, Stefano Salvatore, Massimo Candiani

Abstract

Pelvic pain is a common condition which significantly deteriorates health-related quality of life. The most commonly identified causes of pain in the pelvic region are gynaecologic, urologic, gastrointestinal, neurological, and musculoskeletal. However, in up to 33% of patients the source of this symptom is not identified, frustrating both patients and health-care professionals. Pelvic pain may involve both the somatic and visceral systems, making the differential diagnosing challenging. This paper aimed to review the mechanisms involved in pelvic pain perception by analyzing the neural plasticity and molecules which are involved in these complex circuits.

Figures

Figure 1
Figure 1
Innervation of pelvic organs. Sensory axons innervating the vagina reach the spinal cord via pelvic nerves and terminate in sacral spinal cord segments (S2-S4). Axons innervating the uterus travel in the hypogastric nerves and terminate in the thoracolumbar spinal cord segments (T10-L2). The region surrounding the cervix represents a transitional zone and is innervated by fibers that travel in both nerves. Sensory axons from the clitoris and vulva follow the pudendal nerves to sacral spinal cord. Note that sensory information from all pelvic organs may converge on to the same spinal cord neural circuits. DRG (dorsal root ganglia). Reproduced from Jobling et al., 2014, with permission [61].
Figure 2
Figure 2
Models of alternative possibilities for viscerovisceral cross-sensitization in the DRG neuron. (a) ATP released by a neuron innervating the inflamed uterus acts on a neighboring neuron sensitizing its responses to colonic distention. (b) The same neuron innervates the uterus and colon. Uterus inflammation directly sensitizes the neuron to colonic distention. Reproduced from Chaban, 2012, with permission [62].
Figure 3
Figure 3
Neurogenic inflammation. Neuronal factors released from nociceptor sensory neurons directly drive leukocyte chemotaxis, vascular hemodynamics, and the immune response. When noxious stimuli activate afferent signals in sensory nerves, antidromic axon reflexes are generated that induce the release of neuropeptides at the peripheral terminals of the neurons. These molecular mediators have several inflammatory actions: (1) chemotaxis and activation of neutrophils, macrophages, and lymphocytes to the site of injury and degranulation of mast cells. (2) Signaling to vascular endothelial cells to increase blood flow, vascular leakage, and edema. This also allows easier recruitment of inflammatory leukocytes. (3) Priming of dendritic cells to drive subsequent T helper cell differentiation into Th2 or Th17 subtypes. Reproduced from Chiu et al., 2012, with permission [63].

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