Identification of multisegmental nociceptive afferents that modulate locomotor circuits in the neonatal mouse spinal cord

Abstract

Compared to proprioceptive afferent collateral projections, less is known about the anatomical, neurochemical, and functional basis of nociceptive collateral projections modulating lumbar central pattern generators (CPG). Quick response times are critical to ensure rapid escape from aversive stimuli. Furthermore, sensitization of nociceptive afferent pathways can contribute to a pathological activation of motor circuits. We investigated the extent and role of collaterals of capsaicin-sensitive nociceptive sacrocaudal afferent (nSCA) nerves that directly ascend several spinal segments in Lissauer's tract and the dorsal column and regulate motor activity. Anterograde tracing demonstrated direct multisegmental projections of the sacral dorsal root 4 (S4) afferent collaterals in Lissauer's tract and in the dorsal column. Subsets of the traced S4 afferent collaterals expressed transient receptor potential vanilloid 1 (TRPV1), which transduces a nociceptive response to capsaicin. Electrophysiological data revealed that S4 dorsal root stimulation could evoke regular rhythmic bursting activity, and our data suggested that capsaicin-sensitive collaterals contribute to CPG activation across multiple segments. Capsaicin's effect on S4-evoked locomotor activity was potent until the lumbar 5 (L5) segments, and diminished in rostral segments. Using calcium imaging we found elevated calcium transients within Lissauer's tract and dorsal column at L5 segments when compared to the calcium transients only within the dorsal column at the lumbar 2 (L2) segments, which were desensitized by capsaicin. We conclude that lumbar locomotor networks in the neonatal mouse spinal cord are targets for modulation by direct multisegmental nSCA, subsets of which express TRPV1 in Lissauer's tract and the dorsal column. J. Comp. Neurol. 521:2870-2887, 2013. © 2013 Wiley Periodicals, Inc.

Nanomolar Oxytocin Synergizes with Weak Electrical Afferent Stimulation to Activate the Locomotor CPG of the Rat Spinal Cord In Vitro

“…Thus, there are no data on the effects of oxytocin in integrating afferent inputs into the CPG. The role of primary afferents in modulating the locomotor pattern is linked to the existence of sensory feedbacks evoked during gait to physiologically control, at a pre-synaptic level, incoming inputs to the spinal cord [34], and to convey facilitatory signals to the CPG via multisegmental sacrocaudal afferents [35], even with nociceptive content [36].…”

Modulatory and plastic effects of kinins on spinal cord networks

“…Using the HL preparation, we previously demonstrated that peripheral application of capsaicin leads to a TRPV1‐mediated increase in excitability of locomotor networks. We also demonstrated that TRPV1 in the neonatal mouse spinal cord is restricted to the superficial dorsal horn (Mandadi et al ., , b ). We therefore investigated whether the low dose BK induced sensitization of the dorsal horn is dependent on TRPV1 expressing afferents.…”

“…We have demonstrated that, beginning at birth, molecularly defined nociceptive pathways projecting onto the dorsal horn can potently modulate ventral horn networks that generate locomotion, known as central pattern generators (CPGs) (Mandadi et al . ; a ; b ). However, the actions of BK on B2R and the resulting functional consequences on the sensorimotor networks involved in controlling CPGs are poorly characterized.…”

Staggered multi-site low-frequency electrostimulation effectively induces locomotor patterns in the isolated rat spinal cord

“…Although previous reports point out that also capsaicin-sensitive pain-related fibres are involved in the modulation of ongoing FL, 15 modelling studies have shown that DR electrical stimulation activates the locomotor pattern mainly due to a selective recruitment of multiple fibres carrying tactile and proprioceptive inputs. These fibres are characterized by a wide diameter and low excitation threshold, thus being unable to discriminate small variations in stimulus amplitude.…”