On the basis of dendroarchitecture and cell body shape, complemented with morphometry of dendritic ramification, four major neuronal types were distinguished in lamina I of the spinal cord of the rat. (I) Fusiform spiny cells (39% of impregnated neurons) have longitudinal spindle-shaped perikarya with bipolar, less frequently unipolar, dendritic trees rich in pedicled spines and a thin, beaded longitudinal axon; such neurons occur mainly in the lateral marginal zone. In type IA cells (33% of the total), the dendritic domain occupies a narrow longitudinal area, while in type Ib cells (6%) the polar dendritic trees partly arborize ventrally. Fusiform neurons are considered intrinsic cells connected with the longitudinal afferent plexus in lateral lamina I, and in type IB cells also receiving primary input in the substantia gelatinosa. (II) Multipolar cells (23%) have a dense dendritic arbor originating from numerous primary trunks and they predominate in the medial marginal zone. The dendritic arbor is moderately extended dorsoventrally in type IIA cells and reaches lamina III in the larger type IIB cells. The former possess a variety of spines, axonlike processes and sometimes an unmyelinated axon, and are presumably interneurons, while type IIB cells show a thick tapering axon that is probably myelinated. (III) Flattened aspiny neurons (13%) with a polygonal body flattened in the horizontal plane, and a horizontal dendritic arbor confined to lamina I; these cells predominate in middle lamina I. (IV) Pyramidal neurons (25%) have longitudinally elongated perikarya that bulge into the white matter. The arbor has a large longitudinal and lateromedial spread and includes branches which ramify in the white matter. Types III and IV show the classical lateromedially elongated orientation of the marginal cells of the old literature; they show thick tapering axons and probably make up the bulk of the projection neurons of rat lamina I.

Cutaneous sensory neurons that detect noxious stimuli project to the dorsal horn of the spinal cord, while those innervating muscle stretch receptors project to the ventral horn. DRG11, a paired homeodomain transcription factor, is expressed in both the developing dorsal horn and in sensory neurons, but not in the ventral spinal cord. Mouse embryos deficient in DRG11 display abnormalities in the spatio-temporal patterning of cutaneous sensory afferent fiber projections to the dorsal, but not the ventral spinal cord, as well as defects in dorsal horn morphogenesis. These early developmental abnormalities lead, in adults, to significantly attenuated sensitivity to noxious stimuli. In contrast, locomotion and sensori-motor functions appear normal. Drg11 is thus required for the formation of spatio-temporally appropriate projections from nociceptive sensory neurons to their central targets in the dorsal horn of the spinal cord.

The dorsal spinal cord synthesizes a variety of neuropeptides that modulate the transmission of nociceptive sensory information. Here, we used genetic fate mapping to show that Tlx3 ϩ spinal cord neurons and their derivatives represent a heterogeneous population of neurons, marked by partially overlapping expression of a set of neuropeptide genes, including those encoding the anti-opioid peptide cholecystokinin, pronociceptive Substance P (SP), Neurokinin B, and a late wave of somatostatin. Mutations of Tlx3 and Tlx1 result in a loss of expression of these peptide genes. Brn3a, a homeobox transcription factor, the expression of which is partly dependent on Tlx3, is required specifically for the early wave of SP expression. These studies suggest that Tlx1 and Tlx3 operate high in the regulatory hierarchy that coordinates specification of dorsal horn pain-modulatory peptidergic neurons.

No abstract

No abstract

Chronic pain patients commonly complain of working memory deficits, but the mechanisms and brain areas underlying this cognitive impairment remain elusive. The neuronal populations of the mPFC and dorsal CA1 (dCA1) are well known to form an interconnected neural circuit that iscrucialforcorrectperformanceinspatialmemory-dependenttasks.Inthisstudy,weinvestigatedwhetherthefunctionalconnectivitybetween these two areas is affected by the onset of an animal model of peripheral neuropathic pain. To address this issue, we implanted two multichannel arrays of electrodes in the mPFC and dCA1 of rats and recorded the neuronal activity during a food-reinforced spatial working memory task in a reward-based alternate trajectory maze. Recordings were performed for 3 weeks, before and after the establishment of the spared nerve injury model of neuropathy. Our results show that the nerve lesion caused an impairment of working memory performance that is temporally associated with changes in the mPFC populational firing activity patterns when the animals navigated between decision points-when memory retention was most needed. Moreover, the activity of both recorded neuronal populations after the nerve injury increased their phase locking with respect to hippocampal theta rhythm. Finally, our data revealed that chronic pain reduces the overall amount of information flowing in the fronto-hippocampal circuit and induces the emergence of different oscillation patterns that are well correlated with the correct/incorrect performance of the animal on a trial-by-trial basis. The present results demonstrate that functional disturbances in the fronto-hippocampal connectivity are a relevant cause for pain-related working memory deficits.

The influence of the dorsal reticular nucleus (DRt) on pain behaviour during the formalin test was studied in the rat by lesioning the nucleus through local application of electrical current or quinolinic acid. Animals in which the DRt was lesioned ipsilaterally to the paw injected with formalin spent less time in focused (licking, biting or scratching the injected paw) and total (focused pain behaviour plus protection of the injected paw during movements) pain behaviour, and showed paw-jerks less frequently than non-lesioned animals in both phases 1 and 2 of the test. Animals in which the DRt was lesioned contralaterally to the injected paw presented a decrease in total pain behaviour and number of paw-jerks only during phase 2. The number of superficial (laminae I-II) and deep (laminae III-VI) spinal dorsal horn cells expressing the c-fos proto-oncogene 2 h after subcutaneous injection of formalin was reduced by 34% and 50%, respectively, in animals with an ipsilateral DRt lesion as compared to non-lesioned rats. No differences in c-fos expression were observed after lesioning the DRt contralateral to the formalin injection. The results indicate that the DRt is involved in the facilitation of nociception during the formalin test by enhancing the response capacity of dorsal horn neurons to noxious stimulation. It is suggested that the pronociceptive action of the DRt is mediated by the reciprocal connections it establishes with the spinal dorsal horn.

No abstract