Response properties of dorsal root reflexes in cutaneous C fibers before and after intradermal capsaicin injection in rats

C fiber dorsal root reflexes (DRR) contribute to neurogenic inflammation and possibly also to touch-evoked pain (allodynia) induced by intradermal capsaicin. The responses of C fibers in the sural nerve to graded mechanical stimuli before and following intradermal capsaicin were studied in 39 adult male rats. Two-thirds of 111 fibers were without spontaneous activity, while the remaining fibers averaged 1.41+/-0.25 spontaneous antidromic spikes per second. Among the quiescent C fibers only two had excitatory receptive fields, whereas the active C fibers showed three patterns of activity, an excitatory response, an inhibitory response, or no response to mechanical stimulation. The excitatory responses were to high intensity mechanical stimuli alone, while inhibitory responses were evoked in a graded fashion by both noxious and innocuous mechanical stimuli. Intradermal injection of capsaicin increased spontaneous and evoked DRRs in all C fibers with excitatory responses to mechanical stimuli, but none acquired responses to innocuous stimuli. Capsaicin initially produced inhibition of spontaneous activity in C fibers with inhibitory or no receptive fields, but this later resumed and achieved a rate higher than baseline. Mechanical stimuli re-applied following the resumption of spontaneous discharges failed to produce any response. Spontaneous DRRs were increased by topical application of 1 mM beta-alanine (a competitive antagonist for GABA transporters) and abolished by ipsilateral spinal nerve L5 lesion, verifying antidromic origin. The role of C fiber DRRs in normal sensory transmission and during hyperalgesia is discussed.     

Dorsal root reflexes and cutaneous neurogenic inflammation after intradermal injection of capsaicin in rats

The role of dorsal root reflexes (DRRs) in acute cutaneous neurogenic inflammation induced by intradermal injection of capsaicin (CAP) was examined in anesthetized rats. Changes in cutaneous blood flow (flare) on the plantar surface of the foot were measured using a laser Doppler flowmeter, and neurogenic edema was examined by measurements of paw thickness. To implicate DRRs in neurogenic inflammation after CAP injection, the ipsilateral sciatic and femoral nerves were sectioned, dorsal rhizotomies were performed at L(3-)-S(1), and antagonists of GABA or excitatory amino acid receptors were administered intrathecally. Intradermal injection of CAP evoked a flare response that was largest at 15-20 mm from the injection site and that spread >30 mm. Acute transection of the sciatic and femoral nerves or dorsal rhizotomies nearly completely abolished the blood flow changes 15-20 mm from the CAP injection site, although there was only a minimal effect on blood flow near the injection site. These procedures also significantly reduced neurogenic edema. Intrathecal bicuculline, 6-cyano-7-nitroquinoxaline-2,3-dione, (CNQX) or D(-)-2-amino-7-phosphonoheptanoic acid (AP7), but not phaclofen, also reduced dramatically the increases in blood flow 15-20 mm from the CAP injection site, but had only a minimal effect on blood flow near the injection site. Neurogenic edema was reduced by the same agents that reduced blood flow. Multiunit DRRs recorded from the central stumps of cut dorsal rootlets in the lumbar spinal cord were enhanced after CAP injection. This enhanced DRR activity could be reduced significantly by posttreatment of the spinal cord with bicuculline, CNQX or AP7, but not phaclofen. It is concluded that peripheral cutaneous inflammation induced by intradermal injection of CAP involves central nervous mechanisms. DRRs play a major role in the development of neurogenic cutaneous inflammation, although a direct action of CAP on peripheral nerve terminals or the generation of axon reflexes also may contribute to changes in the skin near the injection site.     

Sympathetic modulation of activity in Adelta- and C-primary nociceptive afferents after intradermal injection of capsaicin in rats

Neuropathic and inflammatory pain can be modulated by the sympathetic nervous system. In some pain models, sympathetic postganglionic efferents are involved in the modulation of nociceptive transmission in the periphery. The purpose of this study is to examine the sensitization of Adelta- and C-primary afferent nociceptors induced by intradermal injection of capsaicin (CAP) to see whether the presence of sympathetic efferents is essential for the sensitization. Single primary afferent discharges were recorded from the tibial nerve after the fiber types were identified by conduction velocity in anesthetized rats. An enhanced response of some Adelta- and most C-primary afferent fibers to mechanical stimuli was seen in sham-sympathectomized rats after CAP (1%, 15 mul) injection, but the enhanced responses of both Adelta- and C-fibers were reduced after sympathetic postganglionic efferents were removed. Peripheral pretreatment with norepinephrine by intraarterial injection could restore and prolong the CAP-induced enhancement of responses under sympathectomized conditions. In sympathetically intact rats, pretreatment with an alpha(1)-adrenergic receptor antagonist (terazosin) blocked completely the enhanced responses of C-fibers after CAP injection in sympathetically intact rats without significantly affecting the enhanced responses of Adelta-fibers. In contrast, a blockade of alpha(2)-adrenergic receptors by yohimbine only slightly reduced the CAP-evoked enhancement of responses. We conclude that the presence of sympathetic efferents is essential for the CAP-induced sensitization of Adelta- and C-primary afferent fibers to mechanical stimuli and that alpha(1)-adrenergic receptors play a major role in the sympathetic modulation of C-nociceptor sensitivity in the periphery.     

Sensitization of dorsal root reflexes in vitro and hyperalgesia in neonatal rats produced by capsaicin

The maturation of dorsal root reflexes (DRRs) in lumbar roots was characterized in neonatal rats at 1, 2 and 3 weeks after birth using an in vitro isolated spinal cord preparation with attached dorsal roots and dorsal root ganglia (DRG). Changes of DRRs in rats of increasing age were also tested by administration of capsaicin to the DRG and related to spinal mechanisms of hyperalgesia by defining the behavioral responses of neonatal rats to intradermal capsaicin. DRRs evoked by stimulating the adjacent root in 1 week old rats are characterized by highly desynchronized waveforms with power spectra concentrated at frequencies greater than 200 Hz. DRRs in 1 week old rats show very little change in amplitude or area with increasing afferent stimulation strength. In contrast DRRs in 2 and 3 weeks old rats are highly synchronized with power concentrated at frequencies less than 100 Hz and show a graded increase in amplitude and area with increasing stimulus strength. The recovery of DRR amplitude in a paired pulse stimulus protocol is faster in 1 week rats than in 2 or 3 weeks old rats. Finally, DRRs in 2 and 3 week old rats show increased amplitude and area following application of capsaicin to the DRG of the stimulating root whereas those in 1 week old rats do not. These changes parallel the behavioral responses of neonatal rats as 2 and 3 weeks old rats show secondary mechanical hyperalgesia following intradermal capsaicin, but 1 week old rats do not. Our data indicate that the spinal circuitry for DRRs in the neonatal period undergoes rapidly dynamic development in the rat. This development is sufficiently rapid that mechanisms of spinal sensitization induced by capsaicin can be studied in rats 2 weeks old and older.     

NMDA or non-NMDA receptor antagonists attenuate increased Fos expression in spinal dorsal horn GABAergic neurons after intradermal injection of capsaicin in rats

GABAergic neurons play an important role in the generation of primary afferent depolarization, which results in presynaptic inhibition and, if large enough, triggers dorsal root reflexes. Recent electrophysiological studies by our group have suggested that increased excitation of spinal GABAergic neurons by activation of N-methyl-D-aspartate (NMDA) and non-NMDA receptors following intradermal injection of capsaicin results in the generation of DRRs that contribute to neurogenic inflammation. The present study was to determine if changes in the expression of Fos protein occur in GABAergic neurons in the lumbosacral spinal cord following injection of capsaicin into the glabrous skin of one hind paw of anesthetized rats and if pretreatment with an NMDA receptor antagonist, D-(-)-2-amino-7-phosphonoheptanoic acid (AP7) or a non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocks Fos expression in these neurons. The experiments used western blots and immunofluorescence double labeling staining following capsaicin or vehicle injection. Western blots showed that Fos protein was increased on the ipsilateral side in spinal cord tissue 0.5 h after capsaicin injection. Pretreatment with AP7 or CNQX caused a decrease in capsaicin-induced Fos expression. Immunofluorescence double labeling showed that the proportion of Fos-positive GABAergic neuronal profiles was significantly increased following capsaicin injection (48.8+/-4.8%) compared to the vehicle injection (23.8+/-5.1%) in superficial laminae on the ipsilateral side in lumbosacral spinal cord (P<0.05). However, when the spinal cord was pretreated with AP7 (5 microg) or CNQX (0.2 microg), only 9.1+/-0.6% or 7.1+/-0.8% of GABA-immunoreactive neuronal profiles were stained for Fos following capsaicin injection. The blockade of the capsaicin-evoked Fos staining was dose-dependent. These findings suggest that GABAergic neurons take part in dorsal horn circuits that modulate nociceptive information and that the function of GABAergic neurons following capsaicin injection is partially mediated by NMDA and non-NMDA receptors.     

Role of protein kinase A in phosphorylation of NMDA receptor 1 subunits in dorsal horn and spinothalamic tract neurons after intradermal injection of capsaicin in rats

Protein phosphorylation is a major mechanism for regulation of N-methyl-D-aspartate (NMDA) receptor function. The NMDA receptor 1 subunit (NR1) is phosphorylated by protein kinase A (PKA) on serine 890 and 897. We have recently reported that there is enhanced phosphorylation of NR1 on serine 897 in dorsal horn and spinothalamic tract (STT) neurons after intradermal injection of capsaicin (CAP) in rats [Zou et al. (2000) J. Neurosci. 20, 6989-6997]. Whether or not this phosphorylation, which develops during central sensitization following CAP injection, is mediated by PKA remains to be determined. In this study, western blots and immunofluorescence staining were employed to observe if pretreatment with a PKA inhibitor, N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, HCl (H89), blocks the enhanced phosphorylation of NR1 on serine 897 following injection of CAP into the glabrous skin of one hind paw of anesthetized rats. Western blots showed that pretreatment with H89 caused a decrease in CAP-induced phosphorylation of NR1 protein in spinal cord segments L(4)-S(1). In experiments using immunofluorescence staining, the numbers of phospho-NR1-like immunoreactive (p-NR1-LI) neurons seen after CAP injection were significantly decreased in the dorsal horn of the L(4)-L(5) segments on the side ipsilateral to the injection after PKA was inhibited. When STT cells were labeled by microinjection of the retrograde tracer, fluorogold, we found that the proportion of p-NR1-LI STT cells on the side ipsilateral to the injection in the superficial laminae of spinal cord segments L(4)-L(5) was markedly reduced when H89 was administered intrathecally before CAP injection. However, the proportion of p-NR1-LI STT cells in deep laminae was unchanged unless the PKC inhibitor, chelerythrine chloride, was co-administered with H89. Combined with our previous findings, the present results indicate that NR1 in spinal dorsal horn neurons, including the superficial dorsal horn STT cells, is phosphorylated following CAP injection and that this phosphorylation is due to the action of PKA. However, the phosphorylation of deep STT cells involves both PKA and PKC.     

Role of calcitonin gene-related peptide in the sensitization of dorsal horn neurons to mechanical stimulation after intradermal injection of capsaicin

This study was designed to assess the role of calcitonin gene-related peptide (CGRP) and its receptor in the sensitization of dorsal horn neurons induced by intradermal injection of capsaicin in rats. Extracellular recordings were made from wide dynamic range (WDR) dorsal horn neurons with receptive fields on the hindpaw in the lumbar enlargement of anesthetized rats. The background activity and responses to brushing, pressing, and pinching the skin were assessed. A postsuperfusion or a presuperfusion of CGRP(8-37) paradigm was followed. When tested 30 min after capsaicin injection, there was an increase in background activity and responses to brush, press, and pinch applied to the receptive field. Superfusion of CGRP(8-37) into the spinal cord at 45 min after capsaicin injection significantly reversed the increased background activity and responses to brush, press, and pinch applied to the receptive field. On the other hand, spinal superfusion of CGRP(8-37) prior to capsaicin injection prevented the increased background activity and responses to brush, press, and pinch of WDR neurons that occurred following capsaicin injection in control experiments. A sensitization of spinal dorsal horn neurons could also be induced by superfusion of the spinal cord with CGRP. The effect could be blocked by CGRP(8-37) dose-dependently. Collectively, these results suggest that CGRP and its receptors are involved in the spinal cord central sensitization induced by intradermal injection of capsaicin.     

Sympathetic influence on capsaicin-evoked enhancement of dorsal root reflexes in rats

A series of experiments by our group suggest that the initiation and development of neurogenic inflammation in rats are mainly mediated by dorsal root reflexes (DRRs), which are conducted centrifugally from the spinal dorsal horn in primary afferent nocieptors. In this study, DRRs were recorded in anesthetized rats from single afferent fibers in the proximal ends of cut dorsal root filaments at the L4-L6 level and tested for responses to intradermal injection of capsaicin. Sympathectomy combined with pharmacological manipulations were employed to determine if the capsaicin-evoked enhancement of DRRs was subject to sympathetic modulation. DRRs could be recorded from both myelinated (Abeta and Adelta) and unmyelinated (C) afferent fibers. After capsaicin was injected intradermally into the plantar foot, a significant enhancement of DRRs was seen in C- and Adelta-fibers but not in Abeta-fibers. This enhancement of DRRs evoked by capsaicin injection was almost completely prevented by sympathectomy. However, if peripheral alpha1-adrenoceptors were activated by intra-arterial injection of phenylephrine, the enhancement of DRRs evoked by capsaicin could be restored, whereas no such restoration was seen following pretreatment with an alpha2-adrenoceptor agonist, UK14,304. Under sympathetically intact conditions, the enhanced DRRs following capsaicin injection could be blocked by administration of terazosin, an alpha1-adrenoceptor antagonist, but not by administration of yohimbine, an alpha2-adrenoceptor antagonist. These results provide further evidence that the DRR-mediated neurogenic inflammation depends in part on intact sympathetic efferents acting on peripheral alpha1-adrenoceptors, which augment the sensitization of primary afferent nociceptors induced by capsaicin injection, helping trigger DRRs that produce vasodilation.     

Minocycline inhibits the enhancement of antidromic primary afferent stimulation-evoked vasodilation following intradermal capsaicin injection

Neurogenic inflammation is induced by inflammatory mediators released in peripheral tissue from primary afferent nociceptors. Our previous studies suggest that neurogenic inflammation induced by intradermal injection of capsaicin results from the enhancement of dorsal root reflexes (DRRs), which involve antidromic activation of dorsal root ganglion (DRG) neurons. Numerous studies have reported the important role of glial modulation in pain. However, it remains unclear whether glial cells participate in the process of neurogenic inflammation-induced pain. Here we tested the role of DRG satellite glial cells (SGCs) in this process in anesthetized rats by administration of a glial inhibitor, minocycline. Electrical stimuli (ES, frequency 10 Hz; duration 1 ms; strength 3 mA) were applied to the cut distal ends of the L4–5 dorsal roots. The stimuli evoked antidromic action potentials designed to mimic DRRs. Local cutaneous blood flow in the hindpaw was measured using a Doppler flow meter. Antidromic ES for 10 min evoked a significant vasodilation that could be inhibited dose-dependently by local administration of the calcitonin gene-related peptide receptor antagonist, CGRP8–37. Pretreatment with capsaicin intradermally injected into the hindpaw 2 h before the ES enhanced greatly the vasodilation evoked by antidromic ES, and this enhancement could be reversed by minocycline pretreatment. Our findings support the view that neurogenic inflammation following capsaicin injection involves antidromic activation of DRG neurons via the generation of DRRs. Inhibition of neurogenic inflammation by minocycline is suggested to be associated with its inhibitory effect on SGCs that are possibly activated following capsaicin injection.     

Cardio-respiratory reflexes evoked by phenylbiguanide in rats involve vagal afferents which are not sensitive to capsaicin

Aim: Stimulation of pulmonary C fibre receptors by phenylbiguanide (PBG, 5-HT₃ agonist) produces hypotension, bradycardia and tachypnoea or apnoea. However, tachypnoeic or apnoeic responses are not consistent. Therefore, this study was undertaken to delineate the actions of PBG on respiration and compared with those evoked by capsaicin (TRPV1 agonist). Methods: Blood pressure, respiratory excursions and ECG were recorded in urethane anaesthetized adult rats. The effect of PBG or capsaicin was evaluated before and after ondansetron (5-HT₃ antagonist), capsazepine (TRPV1 antagonist) or bilateral vagotomy. In addition, their effect on vagal afferent activity was also evaluated. Results: Bolus injection of PBG produced concentration-dependent (0.1–100 μg kg⁻¹) hypotensive and bradycardiac responses, while there was tachypnoea at lower concentrations (0.1–3 μg kg⁻¹) and apnoea at higher concentrations (10–100 μg kg⁻¹). After vagotomy or after exposure to ondansetron both tachypnoeic and apnoeic responses were abolished along with cardiovascular responses. However, capsazepine (3 mg kg⁻¹) did not block the PBG-induced reflex responses. Capsaicin (0.1–10 μg kg⁻¹), on the other hand, produced a concentration-dependent apnoea, hypotension and bradycardia but tachypnoea was not observed. Ondansetron failed to block the capsaicin-induced reflex response while bilateral vagotomy abolished bradycardiac and hypotensive responses and attenuated the apnoeic response. In another series, vagal afferent activity and cardio-respiratory changes evoked by PBG were blocked by ondansetron. However, capsaicin failed to activate the PBG-sensitive vagal afferents even though cardio-respiratory alterations were observed. Conclusions: The present observations indicate that PBG produced tachypnoea at a lower concentration and apnoea at a higher concentration involving vagal afferents which are different from those excited by capsaicin.     

Sympathetic modulation of acute cutaneous flare induced by intradermal injection of capsaicin in anesthetized rats

Much of the acute cutaneous neurogenic inflammation after intradermal injection of capsaicin (CAP) in rats is mediated by dorsal root reflexes (DRRs), which cause the release of inflammatory agents from primary afferent terminals. Sympathetic efferents modulate neurogenic inflammation by interaction with primary afferent terminals. In this study, we examined if DRR-mediated flare after CAP injection is subject to sympathetic modulation. Changes in cutaneous blood flow on the plantar surface of the foot were measured using a laser Doppler flow meter. After CAP injection, cutaneous flare spread more than 20 mm away from the site of CAP injection. However, this CAP-induced flare was significantly reduced after surgical sympathectomy. Decentralization of postganglionic neurons did not affect the flare induced by CAP injection. If the foot of sympathectomized rats was pretreated with an alpha(1)-adrenoceptor agonist (phenylephrine) by intra-arterial injection, the spread of flare induced by CAP injection could be restored. However, if the spinal cord was pretreated with a GABA(A) receptor antagonist, bicuculline, to prevent DRRs, phenylephrine no longer restored the CAP-evoked flare. An alpha(2)-adrenoceptor agonist (UK14,304) did not affect the CAP-evoked flare in sympathectomized rats. In sympathetically intact rats, blockade of peripheral alpha(1)-adrenoceptors with terazosin profoundly reduced the flare induced by CAP injection, whereas blockade of peripheral alpha(2)-adrenoceptors by yohimbine did not obviously affect the flare. Therefore the pathogenesis of acute neurogenic inflammation in the intradermal CAP injection model depends in part on intact sympathetic efferents and alpha(1)-adrenoceptors. Peripheral alpha(1)-adrenoceptors thus modulate the ability of capsaicin sensitive afferents to evoke the release of inflammatory agents from primary afferents by DRRs.     

Long-range projections of Adelta primary afferents in the Lissauer tract of the rat

Electrical microstimulation has been used to activate fine myelinated primary afferents running within the Lissauer tract. Stimulation of the tract at the L2/L3 border produced antidromic volleys which were recorded on the dorsal roots of more caudal spinal segments. Antidromic volleys were present in all cases for roots as far caudal as the S2 segment (L3, n=12; L4, n=6; L5, n=6; L6, n=9; S1, n=3; S2, n=6; observations in a total of 15 rats). These fibres were collaterals of primary afferents with conduction velocities in the dorsal root of up to 17.3+/-2.3 ms(-1) (mean+/-S.D., n=6; range 14-20 ms(-1)). Conduction velocities within the Lissauer tract were slower; the fastest contributing fibres had conduction velocities of 9.2+/-2.2 ms(-1) (range 6-12 ms(-1)). Lesions of the Lissauer tract caudal to the stimulation site abolished the volleys on roots lying caudal to the lesion. Most previous works have suggested that primary afferents project in the Lissauer tract for only one or two spinal segments. The present study shows that some fibres project rostrally for up to seven spinal segments (L2-S2).     

Dorsal root potentials and dorsal root reflexes: a double-edged sword

 The nature of dorsal root reflexes (DRRs) and their possible role in peripheral inflammation and the consequent hyperalgesia are reviewed. The history of DRRs and the relationship of DRRs to primary afferent depolarization and presynaptic inhibition in pathways formed by both large and fine afferents are discussed. Emphasis is placed on the mechanisms underlying primary afferent depolarization, including the anatomical arrangement of the synapses involved, how depolarization can result in inhibition by decreasing transmitter release, the role of excitatory amino acids and GABA, the manner in which the equilibrium potential for chloride ions is determined in primary afferent fibers, and forms of presynaptic inhibition that do not utilize GABA_A receptors. There is then a discussion of neurogenic inflammation, including the role of the release of neuropeptides such as substance P and calcitonin gene-related peptide from sensory nerve endings. Evidence is reviewed that links DRRs to a substantial part of the swelling of the knee joint in acute experimental arthritis and to the flare reaction in the skin following intradermal injection of capsaicin. Possible mechanisms by which the level of DRR activity might be enhanced following inflammation are suggested. The consquences of this increase in DRRs may include exacerbation of hyperalgesia as well as of peripheral inflammation. The conversion of an inhibitory process, presynaptic inhibition, to an excitatory one by DRRs can thus lead to pathological consequences. Received: 16 March 1998 / Accepted: 22 September 1998     

Reactive changes in dorsal roots and dorsal root ganglia after C7 dorsal rhizotomy and ventral root avulsion/replantation in rabbits

Current surgical treatment of spinal root injuries aims at reconnecting ventral roots to the spinal cord while severed dorsal roots are generally left untreated. Reactive changes in dorsal root ganglia (DRGs) and in injured dorsal roots after such complex lesions have not been analysed in detail. We studied dorsal root remnants and lesioned DRGs 6 months after C7 dorsal rhizotomy, ventral root avulsion and immediate ventral root replantation in adult rabbits. Replanted ventral roots were fixed to the spinal cord with fibrin glue only or with glue containing ciliary neurotrophic factor and/or brain-derived neurotrophic factor. Varying degrees of degeneration were observed in the deafferented dorsal spinal cord in all experimental groups. In cases with well-preserved morphology, small myelinated axons extended into central tissue protrusions at the dorsal root entry zone, suggesting sprouting of spinal neuron processes into the central dorsal root remnant. In lesioned DRGs, the density of neurons and myelinated axons was not significantly altered, but a slight decrease in the relative frequency of large neurons and an increase of small myelinated axons was noted (significant for axons). Unexpectedly, differences in the degree of these changes were found between control and neurotrophic factor-treated animals. Central axons of DRG neurons formed dorsal root stumps of considerable length which were attached to fibrous tissue surrounding the replanted ventral root. In cases where gaps were apparent in dorsal root sheaths, a subgroup of dorsal root axons entered this fibrous tissue. Continuity of sensory axons with the spinal cord was never observed. Some axons coursed ventrally in the direction of the spinal nerve. Although the animal model does not fully represent the situation in human plexus injuries, the present findings provide a basis for devising further experimental approaches in the treatment of combined motor/sensory root lesions.     

Rhythmic fluctuations of dorsal root potentials and antidromic discharges of primary afferents during fictive locomotion in the cat

1. This study examines rhythmical activity of primary afferents occurring during "fictive" locomotion in decorticate paralyzed cats. Oscillations of the dorsal root potential (DRP) at the frequency of the locomotor rhythm have been observed at the lumbosacral and cervical levels. In addition, rhythmic antidromic discharges of primary afferent units have been recorded from the proximal stumps of cut dorsal root filaments. A detailed study of the relationships between the DRP fluctuations, the antidromic discharges, and the locomotor activity monitored by recording extensor and flexor muscle nerves is presented. 2. Typical DRP recordings from both lumbosacral and cervical levels show two negative waves (N1 and N2) separated by positive troughs (P1 and P2) in each locomotor cycle. Linear regression analyses indicate that the first negative wave (which generally has the largest amplitude) is related to the flexor activity whereas the second is related to the extensor activity. The relative amplitude of the two negative waves may vary without apparent concomitant changes in the recorded flexor or extensor motor nerves. The positive troughs occur respectively close to the period of transition between flexor and extensor activities and between extensor and flexor activities. 3. DRPs of similar period and amplitude can be observed in different ipsilateral roots recorded simultaneously. The DRPs recorded bilaterally from the same segment have the same periodicity but are out-of-phase. Point-to-point variations of amplitude in bilaterally recorded roots are not correlated. This suggests that the polarization of primary afferents on one side is mainly related to the locomotor events on that side. DRPs have been recorded in cats spinalized at Th13 and injected with nialamide and l-DOPA. This suggests that although the supraspinal contribution may be important, at least part of the DRPs may result from locomotor activity within the spinal cord itself. 4. A salient finding in our experiments was that of rhythmic antidromic unit discharges in the proximal stump of cut dorsal root filaments. Of the 194 units recorded, 19% (37/194) discharged in distinct bursts occurring at fixed times in the locomotor cycle. The majority of the units discharged either one burst during the period of flexor or extensor activity or one burst during one of the two periods of transition. Three units discharged two bursts per locomotor cycle. The frequency of the antidromic discharges of some units in one limb were also found to be modulated by stimulation of the skin or passive manipulation of the limbs.(ABSTRACT TRUNCATED AT 400 WORDS)     

Urethral flow-responsive afferents in the cat sacral dorsal root ganglia

Although sensory feedback from the urethra plays an integral role in the regulation of lower urinary tract function, little is known about the properties of flow-responsive primary afferent neurons. The purpose of this study was to characterize the activity of sacral afferents that responded to fluid flow through the urethra. Single neuron action potentials were recorded extracellularly from the S1 and S2 dorsal root ganglia in eight cats anesthetized with α-chloralose. 21 of 116 cells responded to urethral flow but not to mechanical palpation of the perineum, 22 responded to both urethral flow and palpation, and 27 responded to palpation only. 34 of the 43 flow-responsive cells exhibited a firing response to 10 ml flow boluses that could be fit using a power function: FR(t) = a × (t)^b + c, where FR is firing rate, t is time, and a, b and c are constants. In all 34 cells the ‘b’ term was negative, indicating that the firing rate slowed over the time course of the urethral flow. In 16 of the 24 cells that were recorded during at least four different flow rates, a power function provided a good fit of the relationship between firing rate and flow rate: FR(flow) = k × (flow)^p + q, where k, p and q are constants. In each of these 16 cells the ‘p’ term was positive, indicating that the firing rate tended to increase with increases in flow rate. These are the first data to characterize the properties of flow-responsive afferents in the cat, and reveal properties that parallel those of other afferents.     

Sensory fiber regeneration after dorsal root ganglion section in rats

Department of Histology, S. M. Kirov Gor'kii Medical Institute. Laboratory of Neuronal Structure of the Brain, Brain Research Institute, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR D. S. Sarkisov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 10, pp. 429–430, October, 1990.     

Monosynaptic and dorsal root reflexes during locomotion in normal and thalamic cats

1. In normal and thalamic walking cats electrical stimulation of muscle nerves via chronically implanted electrodes produced electromyographic (EMG) and neurographic responses that were modulated in amplitude depending on the phase of the step cycle. These responses were examined for possible indications of effects of primary afferent depolarization (PAD) during stepping. 2. Monosynaptic reflexes (MSRs) produced by stimulating the lateral gastrocnemius (LG) and medial gastrocnemius (MG) nerves were recorded as EMGs in MG or LG muscles during treadmill locomotion in normal cats. These heteronymous MSR responses were greatest during the stance (extensor) phase. 3. In the same animals, after decerebration, similar modulation of the heteronymous ankle extensor MSRs occurred during spontaneous locomotion with the use of the same stimulus and recording sites. 4. In both normal and thalamic cats the amplitude of neurogram responses recorded from LG or MG nerve after stimulation of the other muscle nerve varied with phase of stepping but did not parallel the variations of the MSR measured as EMG amplitude in the same muscle. The nerve responses were largest during the flexion phase of the step cycle and had a calculated central latency of 0.6-1.0 ms. These are interpreted as arising from antidromic activity in large-caliber afferent nerve fibers (i.e., dorsal root reflexes). 5. Spontaneous antidromic activity in severed L7 dorsal rootlet fibers to triceps surae was observed in the thalamic cats during episodes of locomotion and was closely correlated with flexion phase EMG activity in semitendinosus, a bifunctional muscle. 6. In decerebrate cats, dorsal root reflexes (DRRs) in severed filaments of L4-L7 dorsal roots were produced by stimulation of saphenous and posterior tibial nerves. These DRRs were always smaller during locomotion than during rest and were smallest during the flexion phase. 7. The short-latency antidromic activity produced in muscle nerves by stimulating heteronymous muscle nerves thus appears to be a DRR produced in Group I terminal arborizations that are depolarized close to threshold during the flexion phase. Such PAD could account for changes in the MSR that do not always parallel the levels of recruitment of the motor pools as manifest by background EMG amplitude.