Axons of Individual Dorsal Horn Neurons Bifurcated to Project in Both the Anterolateral and the Postsynaptic Dorsal Column Systems.

Sensory information stimulates receptors of somatosensory system neurons generating a signal that codifies the characteristics of peripheral stimulation. This information reaches the spinal cord and is relayed to supra-spinal structures through two main systems: the postsynaptic dorsal column-medial lemniscal (DC-ML) and the anterolateral (AL) systems. From the classical point of view, the DC-ML has an ipsilateral ascending pathway to the Gracilis (GRA) or Cuneate (CUN) nuclei and the AL has a contralateral ascending pathway to the ventral posterolateral (VPL) thalamic nucleus. These two systems have been the subject of multiple studies that established their independence and interactions. To analyze the ascending projections of L1-L5 spinal dorsal horn neurons in the rat, two retrograde neuronal tracers were injected into the GRA and the VPL. Additionally, an electrophysiological study was performed by applying electrical stimulation at the GRA or VPL and recording antidromic evoked activity in single unit spinal cord cells. Importantly, a subset of spinal dorsal horn neurons exhibited double staining, indicating that these neurons projected to both the GRA and the VPL. These double-stained neurons were located on both sides of the dorsal horn of the spinal cord. The spinal dorsal horn neurons exhibited antidromic and collision activities in response to both GRA and VPL electrical activation. These results show spinal cord neurons with bifurcated bilateral projections to both the DC-ML and AL systems. Based on these results, we named these neurons bilateral and bifurcated cells.

The role of peripheral vasopressin 1A and oxytocin receptors on the subcutaneous vasopressin antinociceptive effects.

BACKGROUND: Vasopressin (AVP) seems to play a role as an antinociceptive neurohormone, but little is known about the peripheral site of action of its antinociceptive effects. Moreover, AVP can produce motor impairment that could be confused with behavioural antinociception. Finally, it is not clear which receptor is involved in the peripheral antinociceptive AVP effects. METHODS: In anaesthetized rats with end-tidal CO2 monitoring, extracellular unitary recordings were performed, measuring the evoked activity mediated by Aß-, Aδ-, C-fibres and post-discharge. Behavioural nociception and motor impairment were evaluated under subcutaneous AVP (0.1-10 µg) using formalin and rotarod tests. Selective antagonists to vasopressin (V1A R) or oxytocin receptors (OTR) were used. Additionally, vasopressin and oxytocin receptors were explored immunohistochemically in skin tissues. RESULTS: Subcutaneous AVP (1 and 10 µg/paw) induced antinociception and a transitory reduction of the end-tidal CO2 . The neuronal activity associated with Aδ- and C-fibre activation was diminished, but no effect was observed on Aß-fibres. AVP also reduced paw flinches in the formalin test and a transitory locomotor impairment was also found. The AVP-induced antinociception was blocked by the selective antagonist to V1A R (SR49059) or OTR (L368,899). Immunohistochemical evidence of skin VP and OT receptors is given. CONCLUSIONS: Subcutaneous AVP produces antinociception and behavioural analgesia. Both V1a and OTR participate in those effects. Our findings suggest that antinociception could be produced in a local manner using a novel vasopressin receptor located in cutaneous sensorial fibres. Additionally, subcutaneous AVP also produces important systemic effects such as respiratory and locomotor impairment. SIGNIFICANCE: Our findings support that AVP produces peripheral antinociception and behavioural analgesia in a local manner; nevertheless, systemic effects are also presented. Additionally, this is the first detailed electrophysiological analysis of AVP antinociceptive action after subcutaneous administration. The results are reasonably explained by the demonstration of V1A R and OTR in cutaneous fibres.