5-HT5A receptor localization in the rat spinal cord suggests a role in nociception and control of pelvic floor musculature

The 5-HT5A receptor is a seven-transmembrane receptor negatively coupled to adenylate cyclase, whose activation opens K+ channels. The 5-HT5A receptor may thus exert an inhibitory effect on neuronal activity. However, the function of this receptor is still largely unknown, in particular at the spinal level, and this is partly due to lack of specific ligands. Immunocytochemistry using specific anti-5-HT5A antibodies reveals a particularly dense labeling in the two superficial layers of the dorsal horn, suggesting that the 5-HT5A receptor may be involved in the spinal modulation of pain. In addition, a very intense staining in the lumbar dorsolateral nucleus (Onuf nucleus) in both males and females suggests that the 5-HT5A receptor is also involved in micturition through the control of urethral sphincter muscles. Colchicine pretreatment allows the staining of numerous cell bodies in lamina II. Fewer labeled cell bodies are seen in laminae I and III-VI, in the lateral spinal nucleus, and in lamina X. Electron microscope examination of 5-HT5A receptor immunoreactivity in spinal cords from untreated animals confirmed the postsynaptic labeling in all regions studied (dorsal horn, dorsolateral nucleus, and lamina X). The morphological heterogeneity of labeled dorsal horn cell bodies suggests that they belong to functionally distinct neurons (projection neurons and interneurons). In the lumbar dorsolateral nucleus, the labeling is preferentially localized on dendrites, suggesting that in this nucleus 5-HT preferentially acts at the dendritic level. Finally, the dense labeling of postsynaptic specializations suggests that the receptor may be in stock before being addressed to the synaptic differentiation.     

The 5-HT2A receptor is widely distributed in the rat spinal cord and mainly localized at the plasma membrane of postsynaptic neurons

Serotonin (5-HT) plays a major role at the spinal level by modulating most spinal functions through several receptor subtypes including the 5-HT2A receptor. To gain further insight into the cellular role of this receptor, we performed an immunocytochemical study of 5-HT2A receptors in the rat spinal cord, at light and electron microscope levels. The results showed that 5-HT2A receptors were widely distributed in the spinal cord at all segmental levels. Immunolabeling was particularly dense in lamina IX and in the dorsal horn lamina IIi. Immunoreactive cell bodies were numerous in lamina IX, where many but not all motoneurons were labeled, as shown by double labeling with choline acetyltransferase antibodies. Stained cell bodies were also observed in the gray matter. The study at the ultrastructural level focused on the lumbar dorsal horn (laminae I-II) and ventral horn (lamina IX). At both levels, 5-HT2A immunoreactivity was mainly postsynaptic on dendrites and cell bodies. However, a little presynaptic labeling was also observed in axon and axon terminals, some of them containing large granular vesicles attesting to their peptidergic nature. The main result of our study was the "nonsynaptic" plasma membrane localization of 5-HT2A receptors covering a large surface of cell bodies and dendrites, suggesting a paracrine form of action of serotonin. These observations are consistent with a double role (pre- and postsynaptic) for serotonin on these receptors on various cellular targets.     

Changes in cholinergic and opioid receptors in the rat spinal cord,dorsal root and sciatic nerve after ventral and dorsal root lesion

Summary Changes in the distribution of³H-quinuclidinylbenzilate (³ H-QNB),³ H-acetylcholine (³ H-ACh) and³ H-alpha-bungarotoxin (alpha-BTx) binding sites were studied with the use of quantitative in vitro autoradiography in the L4–L6 segments of rats 7 days after ventral L4–L6-rhizotomies and 24 hours after ligation of the dorsal roots L4–L6. The changes in the binding sites of these ligands and of³ H-etorphine binding sites were also studied in the dorsal roots of the rats operated with dorsal root ligation and in the sciatic nerves (around a ligature) in the rats operated with ventral rhizotomy. After ventral rhizotomy³ H-QNB binding sites in the ipsilateral motor neuron area were decreased by about 25% from 100±5 to 73±5 fmol/mg wet weight. After dorsal root ligation³ H-QNB binding sites in the ipsilateral posterior horn were reduced by about 30% from 91±5 to 64±7 fmol/mg wet weight. No significant changes in the binding of the other cholinergic ligands in the spinal cords were observed after the operations. In the dorsal root³ H-alpha-Btx and³ H-etorphine binding sites were higher on the distal side of the ligation (3.5±0.8 and 14±4 fmol/mg wet weight, respectively) than on the proximal side (0.7±0.5 and 2.4±1.2 fmol/mg wet weight, respectively).The same level of³ H-ACh (total, muscarinic and nicotinic) binding was observed on both sides of the ligation. In the sciatic nerve³ H-QNB and total, muscarinic and nicotinic ACh binding sites were higher on the proximal side of the ligation than on the distal side. Except for a small emergence of muscarinic-ACh binding distally to the ligation there were no changes in the number of binding sites in the sciatic nerve after the ventral rhizotomy.Muscarinic antagonist binding sites are probably located on the perikarya of the motor neurons and presynaptically on the primary afferents in the posterior horn and in the dorsal root. Cholinergic agonist binding sites in the spinal cord seem less sensitive to axonal damage than antagonist binding sites. Cholinergic and opioid receptors in peripheral nerves are transported in both anterograde and retrograde directions and their origin seems to be the dorsal root ganglion.     

Immunocytochemical identification of serotonin axonal contacts on characterized neurons in laminae I and II of the cat dorsal horn

Serotonergic pathways from brainstem to spinal cord play an important role in the modulation of pain perception. To establish where that modulation occurs, we examined serotonin-immunoreactive axonal contacts on individually characterized laminae I and II dorsal horn neurons intracellularly filled with horseradish peroxidase. We found serotonin axonal contacts on marginal, stalked, and islet cells. Contacts preferentially occurred on dendritic shafts rather than on spines. Marginal and stalked cells received the heaviest innervation.     

Evidence for spinal origin of neurons synapsing with dorsal root ganglion cells of the cat

The visuotopic structure of primary visual cortex was studied in a group of 7 human volunteers using positron emission transaxial tomography (PETT) and 18F-labeled 2-deoxy-2-fluoro-D-glucose ( [18F]DG). A computer animation was constructed with a spatial structure which was matched to estimates of human cortical magnification factor and to striate cortex stimulus preferences. A lateralized cortical 'checker-board' pattern of [18F]DG was stimulated in primary visual cortex by having subjects view this computer animation following i.v. injection of [18F]DG. The spatial structure of the stimulus was designed to produce an easily recognizable 'signature' in a series of 9 serial PETT scans obtained from each of a group of 7 volunteers. The predicted lateralized topographic 'signature' was observed in 6 of 7 subjects. Applications of this method for further PETT studies of human visual cortex are discussed.     

Functional and morphological features of neurons in the midline region of the caudal spinal cord of the cat

Neurons surrounding and dorsal to the central canal in caudal segments of the cat spinal cord were functionally and morphologically characterized. From electrophysiologically obtained responses these neurons were categorized into 3 functional groups based on excitation by somatic afferent stimulation. Eighteen of 36 units were activated by both low threshold and high threshold primary afferent inputs. Of the remaining 18 units, 9 responded only to innocuous intensities of stimulation and the other 9 were excited selectively by noxious peripheral stimulation. Neurons intracellularly marked with horseradish peroxidase formed a heterogeneous population with respect to perikaryal size, dendritic orientation and dendritic extent, and no evident correlations between functional categories and morphological features were observed in light microscopic analyses. Neurons immediately surrounding the central canal were functionally similar to neurons located in the dorsally adjacent gray matter.     

5-HT1A and 5-HT1B receptors control the firing of serotoninergic neurons in the dorsal raphe nucleus of the mouse: studies in 5-HT1B knock-out mice

The characteristics of the spontaneous firing of serotoninergic neurons in the dorsal raphe nucleus and its control by serotonin (5-hydroxytryptamine, 5-HT) receptors were investigated in wild-type and 5-HT1B knock-out (5-HT1B-/-) mice of the 129/Sv strain, anaesthetized with chloral hydrate. In both groups of mice, 5-HT neurons exhibited a regular activity with an identical firing rate of 0.5-4.5 spikes/s. Intravenous administration of the 5-HT reuptake inhibitor citalopram or the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) induced a dose-dependent inhibition of 5-HT neuronal firing which could be reversed by the selective 5-HT1A antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xane carboxamide (WAY 100635). Both strains were equally sensitive to 8-OH-DPAT (ED50 approximately 6.3 microgram/kg i.v.), but the mutants were less sensitive than wild-type animals to citalopram (ED50 = 0.49 +/- 0.02 and 0.28 +/- 0.01 mg/kg i.v., respectively, P < 0.05). This difference could be reduced by pre-treatment of wild-type mice with the 5-HT1B/1D antagonist 2'-methyl-4'-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carbox yli c acid [4-methoxy-3-(4-methyl-piperazine-1-yl)-phenyl]amide (GR 127935), and might be accounted for by the lack of 5-HT1B receptors and a higher density of 5-HT reuptake sites (specifically labelled by [3H]citalopram) in 5-HT1B-/- mice. In wild-type but not 5-HT1B-/- mice, the 5-HT1B agonists 3-(1,2,5, 6-tetrahydro-4-pyridyl)-5-propoxypyrrolo[3,2-b]pyridine (CP 94253, 3 mg/kg i.v.) and 5-methoxy-3-(1,2,3, 6-tetrahydropyridin-4-yl)-1H-indole (RU 24969, 0.6 mg/kg i.v.) increased the firing rate of 5-HT neurons (+22.4 +/- 2.8% and +13.7 +/- 6.0%, respectively, P < 0.05), and this effect could be prevented by the 5-HT1B antagonist GR 127935 (1 mg/kg i.v.). Altogether, these data indicate that in the mouse, the firing of 5-HT neurons in the dorsal raphe nucleus is under both an inhibitory control through 5-HT1A receptors and an excitatory influence through 5-HT1B receptors.     

Regeneration of transected dorsal root ganglion cell axons into the spinal cord in adult frogs (Xenopus laevis)

The extent of regeneration of the central axonal processes of dorsal root ganglion cells was determined using anterograde horseradish peroxidase histochemistry at 1–12 weeks after dorsal root transection in adult frogs. At 4, 8 and 12 weeks axons were found to have regenerated across the dorsal root entry zone and into the spinal cord.     

Peripheral noxious stimulation induces phosphorylation of the NMDA receptor NR1 subunit at the PKC-dependent site, serine-896, in spinal cord dorsal horn neurons

The N‐methyl‐D ‐aspartate receptor (NMDAR) contributes to central sensitization in the spinal cord and the generation of pain hypersensitivity. NMDAR function is modulated by post‐translational modifications including phosphorylation, and this is proposed to underlie its involvement in the production of pain hypersensitivity in the spinal cord. We now show that a noxious heat stimulus applied to the rat hindpaw induces phosphorylation of the NMDAR NR1 subunit at a protein kinase C (PKC)‐dependent site, serine‐896, in superficial dorsal horn neurons. Phosphorylation of NR1 serine‐896 is essentially absent in the superficial dorsal horn laminae of naïve rats, but there is rapid (< 2 min) induction following a noxious but not innocuous heat stimulus. The number of pNR1‐immunoreactive neuronal profiles in the superficial dorsal horn peaks 30 min after noxious heat stimulation and persists for up to 1 h. pNR1serine896 induction occurs in the endoplasmic reticulum, suggesting that it contributes to trafficking of the receptor from intracellular stores to the membrane. The phosphorylation of the subunit is attenuated by intrathecal injection of the NMDAR antagonist, MK801, suggesting that the NMDAR is involved via a feed‐forward mechanism in its own phosphorylation. The pNR1serine896‐positive neurons are highly co‐localized with PKCdelta and only rarely with PKCgamma. These data provide evidence for an activity‐dependent NMDAR phosphorylation at the PKC‐dependent site, serine‐896, in spinal cord dorsal horn neurons initiated by peripheral noxious stimuli.     

Nociceptive spinothalamic tract and postsynaptic dorsal column neurons are modulated by paraventricular hypothalamic activation

Previously, we demonstrated that stimulation of the paraventricular hypothalamic nucleus diminishes the nociceptive dorsal horn neuronal responses, and this decrease was mediated by oxytocin in the rat. In addition, we have proposed that oxytocin indirectly inhibits sensory transmission in dorsal horn neurons by exciting spinal inhibitory GABAergic interneurons. The main purpose of the present study was to identify which of the neurons projecting to supraspinal structures to transmit somatic information are modulated by the hypothalamic-spinal descending activation. In anaesthetized rats, single-unit extracellular and juxtacellular recordings were made from dorsal horn lumbar segments, which receive afferent input from the toe and hind-paw regions. The projecting spinothalamic tract and postsynaptic dorsal column system were identified antidromically. Additionally, in order to label the projecting dorsal horn neurons, we injected fluorescent retrograde neuronal tracers into the ipsilateral gracilis nucleus and contralateral ventroposterolateral thalamic nucleus. Hence, juxtacellular recordings were made to iontophoretically label the recorded neurons with a fluorescent dye and identify the recorded projecting cells. We found that only nociceptive evoked responses in spinothalamic tract and postsynaptic dorsal column neurons were significantly inhibited (48.1 ± 4.6 and 47.7 ± 8.2%, respectively) and non-nociceptive responses were not affected by paraventricular hypothalamic nucleus stimulation. We conclude that the hypothalamic-spinal system selectively affects the transmission of nociceptive information of projecting spinal cord cells.     

The role of GABA and serotonin in the mediation of raphe-evoked spinal cord dorsal root potentials

The possible involvement of bulbospinal serotonergic systems in the mediation of analgesia has created a need for a better understanding of the influence this system has on neuronal mechanisms in the spinal cord. Therefore, these studies were designed to examine the effects of caudal raphe stimulation on primary afferent depolarization and to determine the role of serotonin (5-HT) and GABA in the mediation of these stimulation-produced effects. Stimulation of the raphe evoked two electrotonically conducted dorsal root potentials (DRP-1 and DRP-2) and two compound action potentials (VRP-1 and VRP-2) which were recorded from the dorsal and ventral roots, respectively. Length constant measurements indicated that DRP-1 was generated in group II and DRP-2 in group I primary afferent fibers. Histological determination of stimulation sites revealed that short-latency potentials (DRP-1 and VRP-1) were evoked from many sites within the caudal brain stem, while the long-latency potentials (DRP-2 and VRP-2) were evoked primarily from sites within the caudal raphe nuclei. The role of serotonin in mediating these evoked potentials was assessed by administering various antagonists of serotonin (cinanserin, methysergide and D-lysergic acid diethylamide). These agents consistently attenuated the long-latency potentials (DRP-2 and VRP-2) but increased the magnitude of DRP-1. The possibility of a GABAergic neuron in the descending systems projecting to primary afferent terminals was studied. Depletion of GABA by semicarbazide blocked DRP-1, but had only a modest effect of DRP-2. However, the putative GABA antagonist, bicuculline, inhibited both DRP-1, and DRP-2. These results suggest that a GABA interneuron is not involved in the bulbospinal serotonergic depolarization of primary afferent terminals. This system appears to constitute a presynaptic filter of afferent input, with the capacity to inhibit different fiber groups.     

Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions

Fractalkine is a unique chemokine reported to be constitutively expressed by neurons. Its only receptor, CX3CR1, is expressed by microglia. Little is known about the expression of fractalkine and CX3CR1 in spinal cord. Given that peripheral nerve inflammation and/or injury gives rise to neuropathic pain, and neuropathic pain may be partially mediated by spinal cord glial activation and consequent glial proinflammatory cytokine release, there must be a signal released by affected neurons that triggers the activation of glia. We sought to determine whether there is anatomical evidence implicating spinal fractalkine as such a neuron-to-glia signal. We mapped the regional and cellular localization of fractalkine and CX3CR1 in the rat spinal cord and dorsal root ganglion, under basal conditions and following induction of neuropathic pain, employing both an inflammatory (sciatic inflammatory neuropathy; SIN) as well as a traumatic (chronic constriction injury; CCI) model. Fractalkine immunoreactivity and mRNA were observed in neurons, but not glia, in the rat spinal cord and dorsal root ganglia, and levels did not change following either CCI or SIN. By contrast, CX3CR1 was expressed by microglia in the basal state, and the microglial cellular concentration was up-regulated in a regionally specific manner in response to neuropathy. CX3CR1-expressing cells were identified as microglia by their cellular morphology and positive OX-42 and CD4 immunostaining. The cellular distribution of fractalkine and CX3CR1 in the spinal circuit associated with nociceptive transmission supports a potential role in the mechanisms that contribute to the exaggerated pain state in these models of neuropathy.     

Autoregulatory properties of dorsal raphe 5-HT neurons: Possible role of electrotonic coupling and 5-HT1D receptors in the rat brain

In the present study, the hypothesis that somatodendritic availability of 5-hydroxytryptamine (5-HT) could be regulated independently of the firing activity of dorsal raphe 5-HT neurons was tested. The 5-HT pathway was electrically stimulated at the level of the ventromedial tegmentum and the ensuing action potentials, recorded in the dorsal raphe, met all criteria for antidromic invasion of 5-HT neurons. The latency of antidromic spikes was current-dependent and the changes in latency were of quantal nature. This observation suggests an electrotonic coupling between 5-HT neurons. Stimulation of the ventromedial tegmentum also induced a decrease in the probability of firing of 5-HT neurons. This reduction in 5-HT neuron firing activity is a 5-HT-mediated response, due to an increased bioavailability of the neurotransmitter in the biophase of somatodendritic 5-HT_1A autoreceptors. The intravenous administration of the 5-HT₁ agonists TFMPP and RU 24969 reduced the duration of suppression of firing induced by the 5-HT-pathway stimulation, without altering the spontaneous firing rate of 5-HT neurons. The effect of TFMPP and RU 24969 on duration of suppression was blocked by (±)mianserin, a drug with high affinity for the rat 5-HT_1D, but not 5-HT_1B, receptors. On the other hand, (−)propranolol, a mixed 5-HT antagonist also blocked the effect of TFMPP. However, the selective 5-HT_1A antagonist (+)WAY 100135 did not alter the effect of TFMPP. These results, in keeping with previous anatomical studies, suggest the existence of electrotonic coupling of 5-HT neurons and indicate that 5-HT release in the rat dorsal raphe nucleus may be controlled independently of firing-regulating 5-HT_1A autoreceptors. They also suggest that 5-HT_1D receptors may play a role in this regulatory function of 5-HT neurons. © 1996 Wiley-Liss, Inc.     

Immunolabelling of the 5-HT 3B receptor subunit in the central and peripheral nervous systems in rodents

The 5-HT(3) receptor is a member of the superfamily of neurotransmitter-gated ion channels involved in fast synaptic signalling and in modulation of neurotransmitter release. As for many other channel receptors, the electrophysiological properties and the functions of the 5-HT(3) receptor are determined by subunit composition of the pentameric channel. Because in situ hybridization did not allow the detection of mRNA encoding the 5-HT(3B) subunit in the rodent central nervous system, or in nearly half of the neurons expressing the 5-HT(3A) subunit in peripheral ganglia, it has been suggested that subunit composition could define at least two 5-HT(3) receptor-expressing neuronal populations. In order to challenge this hypothesis, we have developed polyclonal antibodies directed against a portion of the second intracytoplasmic loop of the mouse 5-HT(3B) subunit. Immunohistochemical analysis in the mouse and the rat revealed that immunolabelling was most prominent in peripheral ganglia, particularly in trigeminal ganglia (TG). In rats, transection or ligature of the infraorbital nerve resulted in a pronounced accumulation of immunoreactive material at the proximal side of the lesioned nerve, and an up-regulation of both subunits in 5-HT(3) receptor-expressing TG neurons. Surprisingly, nearly 100% of neurons expressing 5-HT(3A) subunits were also labelled by anti-5-HT(3B) antibodies. We also detected 5-HT(3B) immunoreactivity in the rat hippocampal CA1 layer and in scattered cortical neurons, indicating that detection of 5-HT(3) subunit mRNA by in situ hybridization might not provide really complete mapping of heteromeric 5-HT(3A/B) vs. homomeric 5-HT(3A) receptors in the peripheral and central nervous systems in rodents.     

Transganglionic regulation of central terminals of dorsal root ganglion cells by nerve growth factor (NGF)

Blockade of axonal transport or transection of the rat sciatic nerve results in transganglionic degenerative atrophy (TDA) of nerve terminals containing fluoride-resistant acid phosphatase (FRAP) in the Rolando substance of the spinal cord. Application of vinblastine (9 micrograms) in a cuff around the sciatic nerve of adult rats blocked the retrograde transport of [125I]NGF in sensory fibers; this amount of vinblastine is identical to the threshold amount that induces TDA. Conversely, application of NGF to the proximal stump of the transected sciatic nerve prevented or delayed the occurrence of TDA as reflected by the maintenance of FRAP in the upper dorsal horn, that otherwise would inevitably disappear following the peripheral nerve lesion. These results suggest that endogenous NGF transported retrogradely in peripheral sensory fibers of the adult rat under normal conditions may be responsible for the regulation of the structural and functional integrity of the central terminals of these FRAP-containing primary sensory neurons and that TDA may be the consequence of the failure of NGF to reach the perikarya of these neurons.     

Expression and localization of insulin receptor in rat dorsal root ganglion and spinal cord

The expression and localization of the insulin receptor (IR) was examined in rat dorsal root ganglia (DRG) and spinal cord using Western blotting, in situ hybridization and immunocytochemistry. Western blotting showed that the molecular weight of the IR beta subunit was higher in PNS than that found in CNS. Both IR mRNA and protein expressions were highest in small-sized sensory DRG neurons and myelinated sensory root fibers expressed higher levels of IR protein than myelinated anterior root fibers. In the spinal cord, IR immunoreactive neurons were present in lateral lamina V and in lamina X, suggesting the presence of IR in nociceptive pathways. Electronmicroscopy of DRGs revealed a polarized localization of the IR in abaxonal Schwann cell membranes, outer mesaxons in close vicinity to tight junctions of both myelinating and non-myelinating Schwann cells and to plasma membranes of sensory neurons. From these findings, we speculate that insulin may play a role in sensory fibers involved in nociceptive function often perturbed in diabetic neuropathy. The high expression of IR localizing to tight junctions of dorsal root mesaxons of DRGs may suggest a regulatory role on barrier functions compensating for the lack of a blood-nerve barrier in dorsal root ganglia. This is consistent with the colocalization of IR with tight junctions of the paranodal barrier and endoneurial endothelial cells in peripheral nerve.     

Dendritic domains of nociceptive-responsive parabrachial neurons match terminal fields of lamina I neurons in the rat

This study investigates, in the anesthetized rat, the dendritic extent of parabrachial (PB) neurons whose nociceptive response to noxious stimuli has been previously recorded with an extracellular micropipette. The PB neurons were then injected with biocytin through the recording micropipette, via a juxtacellular technique. The dendritic arborization of individual PB neurons was carefully compared with the projections of medullary (trigeminal) and spinal lamina I neurons. The latter projections were labeled in separate animals that received injections of Phaseolus vulgaris-leucoagglutinin restricted to the superficial layers of spinal or medullary dorsal horn. We report here that: 1) PB neurons excited chiefly by noxious stimulation of the face have their dendritic tree located primarily within the field of lamina I trigeminal projections, i.e., in the caudal portion of PB area, around the external medial and the caudal part of the external lateral subnuclei; and 2) PB neurons excited chiefly by noxious stimulation of the paw or the tail have their dendritic tree located primarily within the field of lamina I spinal projections, i.e., in PB mid-extent, around the borderline between the external lateral and both the lateral crescent and the superior lateral subnuclei. Our results suggest the presence of an extensive excitatory axodendritic link between lamina I projections and PB nociceptive neurons around the lateral crescent and the external medial subnuclei. These findings strengthen the possibility of involvement of a subgroup of PB neurons in nociceptive processes.     

The effect of peripheral nerve injury on dorsal root potentials and on transmission of afferent signals into the spinal cord

The sciatic nerve adults rats was either cut and ligated or was crushed on one side. The response of the spinal cord to stimulation of the proximal part of the injured nerve was examined at various times after the lesion and compared to the effects of stimulating the intact nerve on the other side. During the first 10 days after nerve section the following measures were not affected: (i) the size of the input volley (compound action potential, CAP, measured on a dorsal root that carried sciatic nerve afferents (L5); (ii) the volley running in the dorsal columns; (iii) the dorsal root potential (DRP) evoked on neighbouring dorsal roots which do not contain sciatic afferents (L2 and L3); (iv) the post-synaptic volleys ascending in the spinal cord. However, by the fourth day after nerve section, there was a decrease of the DRP evoked on the ipsilateral L5 dorsal root by stimulation of the cut nerve. By 10 days this DRP had decreased by 50%. There was also a decrease in the DRP on the L5 root evoked by stimulation of the contralateral intact nerve. Crush lesions of the sciatic nerve did not produce DRP charge. Beginning 10–20 days after nerve cut, there was a decrease in the amplitude of the afferent CAP and of all the measures of central response to the afferent volley. We discuss the possibility that the loss of the DRP may be associated with a disinhibition which results in novel receptive fields which we observe in cord cells deafferented by the peripheral nerve section. The decrease of DRP and the appearance of novel receptive fields do not occur if the peripheral nerve is crushed rather than cut.