Depletion of vesicular zinc in dorsal horn of spinal cord causes increased neuropathic pain in mice.
Zinc enriched (ZEN) neurons and terminals are abundant in the rodent spinal cord. Zinc ions have been suggested to modulate the excitability of primary afferent fibers believed to be important in nociceptive transmission. To test the hypothesis that vesicular zinc concentration is related to neuropathic pain we applied Chung's rodent pain model on BALB/c mice, and traced zinc transporter 3 (ZnT3) proteins and zinc ions with immunohistochemistry and autometallography (AMG), respectively. Under anesthesia the left fifth lumbar spinal nerve was ligated in male mice in order to produced neuropathic pain. The animals were then sacrificed 5 days later. The ZnT3 immunoreactivity was found to have decreased significantly in dorsal horn of fourth, fifth, and sixth lumbar segments. In parallel with the depressed ZnT3 immunoreactivity the amount of vesicular zinc decreased perceptibly in superficial gray matters of especially layer I-IV of the same segments. The transection-induced reduction of vesicular zinc in ZEN terminals of the dorsal horn was synchronic to reduced pain threshold, as measured by von Frey method. In a separate study, we observed intensive zinc selenite precipitation in somata of the smaller spinal ganglion cell, but 5 days after spinal nerve transection zinc precipitation was also found in the lager ganglion cells. The present results indicate that zinc may be involved in pain mechanism in the spinal ganglion level. These results support the hypothesis that vesicular zinc might have a modulatory role for neuropathic pain. Thus, increased pain sensitivity might be related to reduce vesicular zinc level in the dorsal spinal gray matter.
Jo
Seung Mook
SM
Department of Anatomy, Gachon Medical School, Namdong-Gu, Inchon, South Korea.
Danscher
Gorm
G
Schrøder
Henrik D
HD
Suh
Sang Won
SW
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D027682:Cation Transport Proteins; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009437:Neuralgia / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D010147:Pain Measurement; D017288:Pain Threshold; D020671:Posterior Horn Cells / Q000166:cytology / Q000378:metabolism*; D018036:Selenium Compounds / Q000378:metabolism; D013116:Spinal Cord / Q000033:anatomy & histology / Q000378:metabolism; D013127:Spinal Nerves / Q000601:surgery; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*; D017967:Zinc Compounds / Q000378:metabolism
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D018036:Selenium Compounds; C491177:Slc30a3 protein, mouse; D017967:Zinc Compounds; C118202:zinc selenite; D015032:Zinc