title: Sciatic nerve injury induces functional pro-nociceptive chemokine receptors in bladder-associated primary afferent neurons in the rat.
abstract: Visceral sensory afferents during disease or following injury often produce vague, diffuse body sensations, and pain referred to somatic targets. Alternatively, injury due to trauma or disease of somatic nerve targets can also lead to referred pain in visceral targets via a somatovisceral reflex. Both phenomenons are thought to be due to convergence of visceral and somatic afferents within the spinal cord. To investigate a potential peripheral influence for referred pain in visceral targets following somatic nerve injury, we examined whether a sciatic nerve injury known to produce hindpaw tactile hyperalgesia alters the frequency of micturition and the sensitivity of bladder-associated sensory neurons to pro-nociceptive chemokines. Adult female Sprague-Dawley rats received injections of cholera toxin B subunit conjugated to 555 into urinary bladder wall to retrogradely label visceral primary afferent neurons. After 7 days, the right sciatic nerve of these animals was subjected to a lysophosphatidylcholine (LPC)-induced focal demyelination injury. Pre- and post-injury tactile sensitivity in the hind paw and micturition frequency were assayed. Animals were allowed to survive for 14-28 days. Lumbosacral and lumbar dorsal root ganglia (DRG) ipsilateral to the nerve injury were acutely dissociated from sham and nerve injured animals. Bladder wall-associated sensory neurons identified via the retrograde marker were assayed for fluxes in intracellular calcium following administration of pro-nociceptive chemokines. The assayed chemokines included monocyte chemoattractant protein-1 (MCP1/CCL2) and stromal cell derived factor-1 alpha (SDF1/CXCL12). LPC nerve injured animals exhibited tactile hyperalgesia and increased micturition frequency for at least 28 days. Focal demyelination of the sciatic nerve also increased the number of injured L₄L₅ and non-injured L₆-S₂ bladder-associated sensory neurons that responded to MCP1 and SDF1 when compared with sensory neurons derived from uninjured naïve and sham-injured control animals. Taken together, these data suggest that some visceral hypersensitivity states may have a somatic origin. More importantly, nociceptive somatovisceral sensation may be mediated by upregulation of chemokine signaling in visceral sensory neurons.
authors: Department of Urology, Loyola University Health System, Maywood, IL, USA.
authors: R
authors: R
authors: Foster
authors: J
authors: J
authors: Jung
authors: A
authors: A
authors: Farooq
authors: C
authors: C
authors: McClung
authors: M S
authors: MS
authors: Ripsch
authors: M P
authors: MP
authors: Fitzgerald
authors: F A
authors: FA
authors: White
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D018925:Chemokines / Q000494:pharmacology; D002772:Cholera Toxin / Q000378:metabolism; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005260:Female; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000473:pathology; D006930:Hyperalgesia / Q000209:etiology*; D008244:Lysophosphatidylcholines / Q000009:adverse effects; D009475:Neurons, Afferent / Q000378:metabolism*; D017288:Pain Threshold; D051381:Rats; D017207:Rats, Sprague-Dawley; D019707:Receptors, Chemokine / Q000378:metabolism*; D020426:Sciatic Neuropathy / Q000139:chemically induced / Q000150:complications* / Q000473:pathology*; D001743:Urinary Bladder / Q000294:innervation*
chemical_list: D018925:Chemokines; D008244:Lysophosphatidylcholines; D019707:Receptors, Chemokine; D002772:Cholera Toxin; D002118:Calcium