Pain and Plasticity: Spike Sorting Based Approach for Characterizing the Neural Circuitry Mediating Nociceptive Sensitization of the Defensive Strike Response in M. sexta

Abstract

Nociception is the neural process of encoding and processing noxious stimuli; this sensation is transduced by specialized sensory neurons called nociceptors. Activation of nociceptors typically evoke so called “nocifensive behavioral responses,” that are generally aimed at decreasing exposure to the noxious stimulus. Intense activation of nociceptors can result in long lasting changes in the nervous system, as well as a subsequent decrease in the threshold for perceiving and acting upon stimuli as if it were harmful—this persistent change in the organism is nociceptive sensitization. The hornworm, Manduca sexta, displays rapid defensive “striking” behavior that accurately targets the cite of noxious stimulation of the abdominal body wall. Nociceptive sensitization of the defensive strike response has been induced behaviorally and recapitulated in vitro through extracellular electrophysiology, where it appears to be encoded by an increase in the firing frequency occurring within the central nervous system, rather than changes in peripheral nociceptor signaling. The current model proposed by Tabuena et al. (2017), argues that central neural alterations are responsible for the neural correlate of nociceptive sensitization (Tabuena et al., 2017), rather than changes in spiking activity of the primary sensory neurons. While the changes in firing frequency centrally are undisputed, relegating sensitization to the CNS alone may be overly simplistic, as the model is based on the comparison of threshold crossings of purported multiunit activity, rather than of single cell activity of known populations of sensory and/or higher order neurons. Moreover, studies in the vertebrate and invertebrate literature alike have reported retrograde sensitization of primary nociceptors (Parada et al., 2003; Xie et al., 2022; Babcock et al., 2000), mediated by inflammatory signals from the cite of injury, thus complicating the question of central versus peripheral sensitization. Therefore, it is worth re-examining the possibility of presynaptic plasticity as an added contribution to nociceptive sensitization. In this work, we propose leveraging available neuroanatomical data to re-analyze the Tabuena et al. dataset, by performing spike sorting and spike train analyses to tease apart the signals originating from the peripheral sensory neurons to obtain input/output relationships between the identified sensory units and VNC spiking during stimulation. Distinguishing the nociceptor and tracking its stimulus dependent firing is expected to elucidate the contribution of nociceptor activity in nociceptive sensitization. Genentech Scholars Foundation This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.