Visceral Pain Is Referred to Somatic Structures

The initial perception of pain from the viscera is described as diffuse pain along the midline of the trunk (3,2). It is poorly localized relative to the originating tissue. This likely results from the divergent central projection of visceral afferent fibers synapsing with scores of dorsal horn neurons in many segments. As the pain intensifies, it is more clearly referred to somatic tissue. It is perceived as originating from the area of the body that is innervated by somatic primary afferent fibers which project in the same dorsal roots as the visceral afferent fibers innervating the affected organ. One likely cause is convergence of the somatic afferent projection and the visceral afferent projection onto the same dorsal horn neurons: Ruch's convergence-projection theory (33). According to this hypothesis, dorsal horn neurons (or higher in the brain) usually respond to somatic stimuli and rarely respond to stimuli from visceral tissue. Upon persistent afferent input evoked by visceral stimulation, activity in this neuronal circuit is interpreted as arriving over somatic primary afferents and the pain is perceived as originating in somatic tissue (Fig. 3).

Referred pain is generally confined to one or a few dermatomes/myotomes and appears relatively constant with respect to a particular organ. For example, referred pain from angina pectoris is generally perceived in the left arm, shoulder, and jaw. Likewise, referred pain from an inflamed appendix is generally perceived in the right lower quadrant of the abdomen. This hypothesis, however, is inconsistent with the extensively divergent central projection of visceral afferents, which would predict referred pain over a larger portion of the trunk. Because the referred pain is restricted to a few dermatomes, additional factors likely function to confine the region of referred pain. When this balance is disturbed, referred pain is perceived over a larger area and is more intense. For example, the expanded area of referred pain and hyperalgesia in IBS patients (35).

Animal studies support viscerosomatic convergence as a mechanism underlying referred pain (Fig. 3). It is estimated that greater than 90% of dorsal horn neurons that respond to visceral stimuli have somatic receptive fields. Dorsal horn neurons in the lower lumbar/ sacral spinal segments that respond to stimulation of the colon/rectum, bladder, or reproductive organs respond to stimulation of the skin and/or muscle of the hindlimbs, pelvic belly, and perianal area (36-42). Indeed, colonic inflammation in mice evokes withdrawal from mechanical stimuli applied to the lower abdomen at lower thresholds than noninflamed mice, suggesting that animals experience referred pain and hyperalgesia (43).

Likewise, dorsal horn neurons in the thoracic spinal cord that respond to visceral stimulation have convergent somatic receptive fields on the trunk (44-49). The location of the somatic receptive field illustrates two points: first, it is what would be expected based on the location of the dorsal horn neuron with respect to the somatotopic map in the spinal cord. This provides direct support for the hypothesis that referred pain results from convergence of somatic and visceral afferents onto the same dorsal horn neurons. Second, it also points to another paradox in spinal processing. As mentioned previously, the viscera receive dual afferent innervation. In the case of the descending colon and rectum, this is provided by the pelvic nerve projecting to the lumbosacral spinal cord (sacral in man) and the hypogastric/lumbar colonic nerves projecting to the thoracolumbar spinal cord. Experimental balloon distention of the colon and rectum in volunteers evokes referred pain in the sacral dermatomes consistent with input from the pelvic nerve (34,35). Likewise, in rats, sacral dorsal horn neurons that respond to CRD have somatic receptive fields corresponding to sacral dermatomes. However, the thoracolumbar segments receive colonic afferent input via the hypogastric/lumbar colonic

Figure 3 (A) and (B) Volunteers reported the area of referred pain (A) and the pain intensity (B) during the 1st and 10th trial of CRD. By the 10th distention, the area of referred pain expanded and the intensity increased, suggesting central sensitization. Source: Reprinted from Ref. 34. (C-E) Sensitization of a visceroceptive dorsal horn neuron that may underlie visceral hypersensitivity and referred pain. (C) the response to noxious CRD before (top) and following (bottom) colonic inflammation. The response of the cell increased slightly in addition to the significant increase in spontaneous activity. (D) The response to pinch of the convergent somatic receptive field before (top) and following (bottom) colonic inflammation. Because the inflammation was confined to the colon, the somatic primary afferents would not be sensitized. Therefore, the increase in the response to pinch following inflammation must result from central sensitization of the dorsal horn neuron. (E) the size of the convergent receptive field before (black) and after (outlined) colonic inflammation. Surrounding the original receptive field (black) is an area innervated by primary afferents that directly or indirectly connect to the dorsal horn neuron, but have subliminal input incapable of producing action potentials. When the neuron becomes sensitized, the subliminal input now reaches threshold to evoke action potentials, expanding the size of the receptive field. Abbreviation: CRD, colorectal distention.

Figure 3 (A) and (B) Volunteers reported the area of referred pain (A) and the pain intensity (B) during the 1st and 10th trial of CRD. By the 10th distention, the area of referred pain expanded and the intensity increased, suggesting central sensitization. Source: Reprinted from Ref. 34. (C-E) Sensitization of a visceroceptive dorsal horn neuron that may underlie visceral hypersensitivity and referred pain. (C) the response to noxious CRD before (top) and following (bottom) colonic inflammation. The response of the cell increased slightly in addition to the significant increase in spontaneous activity. (D) The response to pinch of the convergent somatic receptive field before (top) and following (bottom) colonic inflammation. Because the inflammation was confined to the colon, the somatic primary afferents would not be sensitized. Therefore, the increase in the response to pinch following inflammation must result from central sensitization of the dorsal horn neuron. (E) the size of the convergent receptive field before (black) and after (outlined) colonic inflammation. Surrounding the original receptive field (black) is an area innervated by primary afferents that directly or indirectly connect to the dorsal horn neuron, but have subliminal input incapable of producing action potentials. When the neuron becomes sensitized, the subliminal input now reaches threshold to evoke action potentials, expanding the size of the receptive field. Abbreviation: CRD, colorectal distention.

nerves. Dorsal horn neurons in these segments have somatic receptive fields on the trunk, separate from the sacral neuron receptive fields. It would then be expected that referred pain should also be perceived as originating in the trunk. This does not occur in normal volunteers, but the area of referred pain expands into the lower abdomen following repetitive colonic distention (Fig. 3A) (34). In contrast, in patients with a functional bowel disorder or an inflammatory bowel disease, referred pain is perceived in the lower abdomen and thorax, as well as in the pelvic area (35). This dermatomal organization of referred pain suggests that acute colorectal pain is processed in the spinal cord segments receiving pelvic nerve afferent input and that following injury or disease, additional processing occurs in the spinal segments receiving afferent input over the hypogastric/lumbar colonic nerves (10).

Alternatively, there may be an interaction between visceral and somatic afferent fibers, which alters somatic sensitivity. Inflammation of the uterus induces localized plasma extravasation in the lower abdomen, demarcating the area of referred pain (50). Several mechanisms have been proposed to account for these data, but the most likely is that visceral afferent fibers project into the spinal cord and induce an antidromically propagating dorsal root reflex in somatic afferent fibers that produce localized neurogenic inflammation in the skin (51). This localized neurogenic inflammation may sensitize nearby somatic afferent fibers evoking a somatic hyperalgesia resulting from a visceral stimulus.

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