Physiological properties of the lamina I spinoparabrachial neurons in the mouse

Abstract

Key points Spinal cord lamina I neurons receiving dense input from nociceptors and projecting to the parabrachial area at the ponto‐mesencephalic junction form the major ascending pain‐related pathway in rodents. Lamina I spinoparabrachial (SPB) neurons have never been characterized in mice, despite the growing and extensive use of this species to understand the contribution of lamina I SPB neurons in chronic pain. The electrophysiological properties of lamina I SPB neurons recorded here in anaesthetized mice are comparable to those of rat or cat, forming a nociceptive and thermoreceptive pathway. It was confirmed ‘on line’ that lamina I SPB neurons that normally encode noxious stimuli can receive input from low threshold mechanoreceptors in certain conditions. The present work indicates that the study of lamina I SPB neurons in vivo could take advantage of the use of genetically modified mice. Abstract Ongoing studies investigating the role of lamina I projection neurons in the generation of chronic pain are mainly based on the use of genetically modified mice. However, lamina I projection neurons have never been physiologically characterized in this species. The present work aimed to fill this gap, and to assess the effect of spinal ‘disinhibition’ that may occur in chronic pain states on the responses of these neurons to light touch. Seventy lamina I spinoparabrachial (SPB) neurons were characterized in anaesthetized mice. These neurons showed low central conduction velocities (<12.4 m s−1) and wide range of responses. Fifty‐six neurons responded equally to noxious mechanical and thermal (heat) stimuli (16% responded consistently to light touch). Modality‐specific neurons responded preferentially to thermal (cold) stimuli (n = 10) and pinch (n = 2), or specifically to heat (n = 2). Spinal bicuculline and strychnine application induced responses to brush in half of the neurons tested, confirming directly the potential connection between low threshold mechanoreceptors and nociceptive‐specific neurons, responsible for mechanical allodynia. Remarkably, the effect of the treatment was highly variable and apparently independent of the initial profile of the neurons. The present data confirm that mice lamina I SPB neurons have the expected characteristics to form a nociceptive and thermoreceptive pathway, but they constitute a highly heterogeneous group. The differential effect of spinal disinhibition observed here suggests that a subgroup of lamina I SPB neurons might be responsible for abnormal pain in pathological conditions, and emphasizes the importance of in vivo recording, a neglected approach.

A labeled-line for cold from the periphery to the parabrachial nucleus

“…In these initial experiments, we recorded from and characterized 34 retrogradely-95 labeled lamina I SPB neurons. Consistent with previous studies (Allard, 2019 None of these SPB neurons responded to heat alone. In contrast, ~25% (8 of 34) 100 responded selectively to cold ( Figures 1B and 1C).…”

“…In particular, extracellular 69 recording from cat and monkey spinal cord in vivo has revealed the existence of 70 spinothalamic tract (STT) neurons that respond to cold stimulation to the skin, but not 71 other somatosensory modalities Craig and Dostrovsky, 2001;Craig 72 and Hunsley, 1991;Craig and Kniffki, 1985;Dostrovsky and Craig, 1996;Zhang et al, 73 2006). In rodent, we and others have described spinoparabrachial (SPB) neurons that are 74 cold-selective (Allard, 2019;Andrew, 2009;Hachisuka et al, 2016). In this study, we 75 identified cold-selective output neurons and then further examined whether they show 76 distinctive features indicative of a distinct subtype of SPB neuron.…”

“…In this regard, one of the key challenges is that 55 most spinal output neurons respond to several types of stimuli. For instance, the majority 56 of temperature-responsive spinal output neurons also respond to mechanical input 57 (Allard, 2019;Craig and Andrew, 2002;Ferrington et al, 1987). 58…”

Selective-cold output through a distinct subset of lamina I spinoparabrachial neurons

“…In particular, extracellular recording from cat and monkey spinal cord in vivo has revealed the existence of spinothalamic tract (STT) neurons that respond to cold stimulation to the skin, but not other somatosensory modalities [11][12][13][14]18,56]. In rodent, we and others have described spinoparabrachial (SPB) neurons that are cold-selective [1,4,22]. However, it remained unclear whether these neurons are cold-selective simply as function of wiring, or whether these cells are a unique cell type, representing a discrete output channel for somatosensation.…”

“…In this regard, one of the key challenges is that most spinal output neurons respond to several types of stimuli. For instance, the majority of temperature-responsive spinal output neurons also respond to mechanical input [1,10,14,21]. Similarly, all spinal output neurons that appear to be tuned for itch also respond to the noxious chemicals mustard oil and capsaicin [5,16,28].…”