Widespread latent hyperactivity of nociceptors outlasts enhanced avoidance behavior following incision injury

Bavencoffe, A. G.; Lopez, E. R.; Johnson, K. N.; Tian, J.; Gorgun, F. M.; Shen, B. Q.; Zhu, M. X.; Dessauer, C. W.; Walters, E. T.

doi:10.1101/2024.01.30.578108

bioRxiv · 10.1101/2024.01.30.578108

Widespread latent hyperactivity of nociceptors outlasts enhanced avoidance behavior following incision injury

Bavencoffe, A. G.·Lopez, E. R.·Johnson, K. N.·Tian, J.·Gorgun, F. M.·Shen, B. Q.·Zhu, M. X.·Dessauer, C. W.·Walters, E. T.

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Abstract

Nociceptors with somata in dorsal root ganglia (DRGs) exhibit an unusual readiness to switch from an electrically silent state to a hyperactive state of tonic, nonaccommodating, low-frequency, irregular discharge of action potentials (APs). Ongoing activity (OA) during this state is present in vivo in rats months after spinal cord injury (SCI), and has been causally linked to SCI pain. OA induced by various neuropathic conditions in rats, mice, and humans is retained in nociceptor somata after dissociation and culturing, providing a powerful tool for investigating its mechanisms and functions. An important question is whether similar nociceptor OA is induced by painful conditions other than neuropathy. The present study shows that probable nociceptors dissociated from DRGs of rats subjected to postsurgical pain (induced by plantar incision) exhibit OA. The OA was most apparent when the soma was artificially depolarized to a level within the normal range of membrane potentials where large, transient depolarizing spontaneous fluctuations (DSFs) can approach AP threshold. This latent hyperactivity persisted for at least 3 weeks, whereas behavioral indicators of affective pain - hindpaw guarding and increased avoidance of a noxious substrate in an operant conflict test - persisted for 1 week or less. An unexpected discovery was latent OA in neurons from thoracic DRGs that innervate dermatomes distant from the injured tissue. The most consistent electrophysiological alteration associated with OA was enhancement of DSFs. Potential in vivo functions of widespread, low-frequency nociceptor OA consistent with these and other findings are to amplify hyperalgesic priming and to drive anxiety-related hypervigilance.

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Bavencoffe, A. G., Lopez, E. R., Johnson, K. N., Tian, J., Gorgun, F. M., Shen, B. Q., Zhu, M. X., Dessauer, C. W., Walters, E. T.. 2024-01-31. Widespread latent hyperactivity of nociceptors outlasts enhanced avoidance behavior following incision injury. https://doi.org/10.1101/2024.01.30.578108

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