Single Wide Dynamic Range Research Articles

Role of the NKCC1 co-transporter in sensitization of spinal nociceptive neurons

The Na+, K+, 2Cl− co-transporter type 1 (NKCC1) plays a pivotal role in hyperalgesia associated with inflammatory stimuli. NKCC1 contributes to maintain high [Cl−]i in dorsal root ganglia (DRG) neurons which cause primary afferent depolarization (PAD) when GABAA receptors are activated. Enhanced GABA-induced depolarization, through increased NKCC1 activity, has been hypothesized to produce orthodromic spike activity of sufficient intensity to account for touch-induced pain. In the present study, we investigate this hypothesis using in vivo electrophysiology on rat dorsal horn neurons; the effects of spinal blockade of NKCC1 on intraplantar capsaicin-induced sensitization of dorsal horn neurons were examined. Single wide dynamic range (WDR) and nociceptive specific (NS) neuron activity in the dorsal horn was recorded using glass microelectrodes in anesthetized rats. Dorsal horn neurons with a receptive field on the plantar surface of the hindpaw were studied. Neuronal responses to mechanical stimuli (brush, von Frey filaments) were recorded ten minutes before intraplantar injection of 0.3ml 0.1% capsaicin (CAP), 40min after CAP and 15min after local application of the NKCC1 blocker bumetanide (BTD; 500μM) on the spinal cord. After CAP, low and high threshold stimulation of the cutaneous receptive field produced a significant enhancement in spike frequency over pre-CAP values in both WDR and NS neurons. Spinal BTD application reduced the spike frequency to baseline levels as well as attenuated the CAP-induced increases in background activity. Our data support the hypothesis that NKCC1 plays an important role in the sensitization of dorsal horn neurons following a peripheral inflammatory insult.

야간 PDS를 위한 광학 흐름과 기울기 방향 히스토그램 이용 방법

자동차 주요 생산국인 우리나라 보행자의 교통사고 사망률은 인구 10만 명 당 5.28명으로서 OECD 평균의 약 2.5배에 달한다. 보행자를 감지하고 운전자에게 경보를 보내주는 시스템이 개발되어 보행자 교통사고를 조금이라도 줄일 수 있다면, 그 자체만으로도 보행자 감지 시스템의 가치는 충분하기 때문에 PDS에 대한 관심이 높아지고 있다. 보행자 교통사고율은 야간에 더 높기 때문에, 야간 보행자 감지 시스템에 주요 자동차 회사들이 관심을 두고 있으나, 그들은 일반적으로 고가의 나이트비젼 또는 복합적 센서를 사용하는 장비를 채택하고 있다. 본 논문에서는 PDS에서 나이트비젼 대신에, 넓은 동적 범위를 갖는 가시 스펙트럼 대역 흑백 카메라 한 대만을 사용하는 야간 보행자 감지 기법을 제안한다. 서로 다른 환경에서 촬영된 야간 동영상들에 대해 실험한 결과, 제안 알고리듬이 에지가 어느 정도 정확하게 검출되는 상황이라면 정확한 보행자 검출 성능을 보였다. The death rate of pedestrian in car accidents in Korea is 2.5 times higher than the average of OECD countries'. If a system that can detect pedestrians and send alarm to drivers is built and reduces the rate, it is worth developing such a pedestrian detection system (PDS). Since the accident rate in which pedestrians are involved is higher at nighttime than in daytime, the adoption of nighttime PDS is being standardized by big auto companies. However, they are usually using night visions or multiple sensors, which are usually expensive. In this paper we suggest a method for nighttime PDS using single wide dynamic range (WDR) monochrome camera in visible spectrum band. In our experiments, pedestrians were accurately detected if only most edges of pedestrians could be obtained.

Ongoing activity in trigeminal wide-dynamic range neurons is driven from the periphery

Ongoing activity of spinal trigeminal neurons is observed under various conditions and suggested to be responsible for ongoing headache. It can be spontaneous, i.e. arising intrinsically from the neuron, or the product of descending influences from other central neurons, or maintained by ongoing afferent input. The aim of the present study was to examine if ongoing activity of neurons in different subnuclei of the spinal trigeminal nucleus is driven from peripheral afferent input. Experiments were performed in Wistar rats anesthetized with isoflurane or Nembutal/urethane. Ongoing activity of single wide-dynamic range (WDR) neurons was recorded with carbon fiber glass microelectrodes in two subnuclei of the spinal trigeminal nucleus: oral (Sp5O) and caudal (Sp5C). Peripheral receptive fields were evaluated using von Frey filaments. Sp5O neurons received peripheral input from facial areas innervated by the mandibular branch of the trigeminal nerve. Units in Sp5C had receptive fields in the surgically exposed dura mater and in facial areas innervated by the ophthalmic and maxillary branch of the trigeminal nerve. Saline or the local anesthetic lidocaine was locally applied onto the exposed dura mater or microinjected into V3 (for Sp5O units) or V1/V2 (for Sp5C units) divisions of the trigeminal ganglion via the infraorbital channel. Local application of lidocaine onto the exposed dura caused mechanical insensitivity of dural receptive fields but not significant decrease in ongoing activity. Microinjection of lidocaine but not saline into the trigeminal ganglion was followed by a substantial decrease in both the receptive field size and the activity of the recorded WDR units. Mechanical insensitivity of receptive fields after trigeminal ganglion blockade was accompanied by the disappearance of ongoing activity. We conclude that the ongoing activity of WDR neurons in the spinal trigeminal nucleus, which may be indicative for processes of sensitization, is driven remotely by ongoing afferent input.

Detection of deterministic behavior within the tissue injury-induced persistent firing of nociceptive neurons in the dorsal horn of the rat spinal cord.

To unravel the temporal features of the peripheral tissue injury induced persistent nociceptive discharge, single wide dynamic range (WDR) unit activity was recorded extracellularly in lumbar dorsal horn of anesthetized rats and interspike interval (ISI) series were obtained. Subcutaneous (s.c.) bee venom (BV) injection induced persistent discharge of spinal WDR neurons and has been well established to be a good model in evaluation of tissue injury induced pain. By applying a more novel approach, i.e., the unstable periodic orbit (UPO) identification method, we detected a family of significant separate UPOs (period-1, 2 and 3 orbits) within the ISI series of BV-induced nociceptive discharge, but not spontaneous background activity of spinal WDR neuron. Furthermore, temporally dynamic changes of UPOs at lower period-1, 2 and 3 for 4 successive time segments within 1 h time course of WDR unit firing showed temporally dynamic changes, i.e., new orbits with longer ISIs emerged and those with shorter ISIs vanished with time change. By using this method we suggest that BV-induced nociceptive discharge of spinal WDR neuron be a kind of deterministic activity and various UPOs may play some role in temporal coding of sensory information.

Induction of long-term potentiation of single wide dynamic range neurones in the dorsal horn is inhibited by descending pathways

Previous studies have shown that long-term potentiation (LTP) in the dorsal horn may be induced by noxious stimuli. In this study it is investigated whether induction of LTP in the dorsal horn may be affected by the descending pathways. Extracellular recordings of wide dynamic range (WDR) neurones in the lumbar dorsal horn in intact urethane-anaesthetized Sprague–Dawley rats were performed, and the electrically evoked neuronal responses in these neurones were defined as A-fibre and C-fibre responses according to latencies. Using a short-term cold block of the thoracic spinal cord, which produced a completely reversible increase of the A-fibre and C-fibre responses, the influence of the descending inhibitory system on the induction of LTP by electrical high-frequency conditioning applied to the sciatic nerve was examined. As previously shown the A-fibre responses were almost unchanged following the conditioning. In contrast, the C-fibre responses following the same conditioning were strongly increased. Thus, a clear LTP of the nociceptive transmission in the dorsal horn was observed following electrical high-frequency conditioning. Interestingly, we found that the LTP was more powerful when the effects of the descending pathways were temporarily eliminated during conditioning. It is concluded that induction of LTP by electrical high-frequency conditioning stimulation, which may be part of the wider term central sensitization, is inhibited by descending pathways.

Excitatory effects of galanin in the spinal cord of intact, anaesthetized rats

The effects of intrathecal galanin on the activity of single wide dynamic range (WDR) spinal dorsal horn neurones were analyzed in anaesthetized adult rats. Aβ-, Aδ- and C-fibres were activated by transcutaneous electrical stimulation which also induced wind-up and post-discharge. Galanin dose-dependently (0.15–15 nmol/50 μl) enhanced Aδ-and C-fibre evoked responses, post-discharge and wind-up. Application of (D-Thr 6, D-Trp 8, 9, 15-ol)-galanin (1–15), a putative antagonist, did not attenuate the enhanced effects evoked by galanin. (D-Thr 6, D-Trp 8, 9, 15-ol)-galanin (1–15) applied alone (0.3–30 nmol/50 μl) to a separate population of neurones inhibited Aβ responses but enhanced post-discharge and wind-up in a similar pattern to galanin. Thus, (D-Thr 6, D-Trp 8, 9, 15-ol)-galanin (1–15) behaved as an agonist in the present experiments. In conclusion, in the spinal cord of the anaesthetized rat, galanin has a purely pro-nociceptive role, since it enhanced responses evoked by high-threshold fibre stimulation, along with post-discharge and wind-up of WDR neurones.

Long-term potentiation in single wide dynamic range neurons induced by noxious stimulation in intact and spinalized rats

Publisher Summary This chapter discusses the long-term potentiation (LTP) in single wide dynamic range (WDR) neurons induced by noxious stimulation in intact and spinalized rats. The wind-up phenomenon shows that neurons respond dynamically to stimulation. Spinal nociceptive neurons increase their responses during a low-frequency constant-intensity train of stimulus pulses (0.8 Hz, C-fiber strength). The wind-up was shown to be most prominent in WDR neurons and natural stimulation of nociceptive C-fibers. Mechanisms of LTP measured in WDR neurons is shown to be segmental but they may be both mono- and polysynaptic. However, there is an indication of a tonic supraspinal descending inhibition preventing the development of an even larger LTP, which were seen in neurons after spinalization. For a quarter of a century, LTP experiments have been done in the hippocampus without confirming the hypothesis that LTP and long-term depression are cellular mechanisms underlying memory. It indicated that long-term memory of neural sensitization, according to Hebb's paradigm, in that WDR neurons strengthen their responses to nociceptive signals after strong nociceptive stimulation.

Effect of spinal morphine after long-term potentiation of wide dynamic range neurones in the rat.

Studies have shown that long-term increase in the excitability of single wide dynamic range neurones in the spinal dorsal horn of rats may be induced after tetanic stimulation to the sciatic nerve. This sensory event is possibly an in vivo counterpart of long-term potentiation, described in the brain. This study investigated whether this phenomenon occurs in the halothane-anesthetized rat and whether the antinociceptive effects of spinally administered morphine are altered when tested on the enhanced activity. Single unit extracellular recordings were made in three different groups of halothane-anesthetized rats (n = 6 in each group). In group 1, the evoked neuronal responses of wide dynamic range neurones by a single electrical stimulus to the peripheral nerve were recorded every 4 min, for 1 h before (baseline) and for 3 h after brief high-frequency conditioning stimulation of the sciatic nerve. In group 2, morphine was applied onto the spinal cord after long-term potentiation had been established. Increasing concentrations of morphine were added until the C fiber-evoked responses were abolished; this was followed by naloxone reversal. In group 3, the same protocol as in group 2 was used except a waiting period substituted for the electrical conditioning. The C fiber-evoked responses were significantly increased (P < 0.001) after conditioning compared with baseline and those in control animals. Further, significantly higher concentrations of morphine (P = 0.008) were needed to abolish the C fiber-evoked responses in tetanized animals than in control animals. Naloxone reversed the effects of morphine to the predrug potentiated baseline in group 2, showing that opioids do not block the maintenance of spinal long-term potentiation. Long-term potentiation of C fiber-evoked responses also can be induced in halothane-anesthetized rats, and morphine seems to have less potency during such conditions. These data suggest that long-term potentiation-like mechanisms may underlie some forms of hyperalgesia associated with a reduced effect of morphine.

Dorsal horn NMDA receptor function is changed after peripheral inflammation

The N-methyl-d-aspartic acid (NMDA) receptor antagonist d,l-2-amino-5-phosphonopentanoic acid (AP5) caused a stronger inhibition of wind-up in single wide dynamic range (WDR) neurons after carrageenan inflammation compared with control neurons without inflammation in the receptive field. This indicates that even a short period (2.5 h) of inflammation induces changes in the function of NMDA receptors. The drug effect was also studied in separate control experiments with few wind-up inducing stimulus trains and little nociceptive input prior to baseline recordings. In these control experiments all evoked responses were reduced by the drug, but the wind-up was significantly increased. A wind-up increase after NMDA receptor antagonism has been reported in two previous studies. Thus, other mechanisms than NMDA receptor stimulation may be more important for the wind-up in not sensitized dorsal horn neurons. As for long-term potentiation, it seems that NMDA receptor antagonists have an increased effect after sensitization. Thus, sensitized and not sensitized dorsal horn neurons may respond differently to an NMDA receptor active drug. In rats nerve stimulation and halothane anaesthesia induced larger evoked responses to afferent stimulation than cutaneous stimulation and urethane anaesthesia, the AP5 effect was however similar.

Natural noxious stimulation can induce long-term increase of spinal nociceptive responses

It is conceivable that plasticity in pain control systems and chronic pain may be due to mechanisms similar to learning. Long-term potentiation (LTP) in the hippocampus is often studied as a model of learning and memory. It has recently been shown that long-term excitation may be induced in single wide dynamic range (WDR) neurones in the spinal dorsal horn of rats after tetanic stimulation to the sciatic nerve. The present study shows that similar long-term changes can also be induced by a severe natural stimulus. Single unit extracellular recordings were made in urethane anaesthetized rats and the firing responses of WDR neurones evoked by a single electrical stimulus to the peripheral nerve were recorded every 4 min. After repeated crushing of tissue (including bone) corresponding to the receptive field of the WDR neurones (the conditioning stimulus) followed by a proximal total peripheral nerve block, the C-fibre evoked responses were increased ( P<0.001) for a 3 h observation period compared with baseline responses and control animals. In control animals the nerve block was applied before the conditioning stimulus. We suggest that a long-term increase of the excitability of WDR neurones may be important for the development of long lasting and chronic pain disorders after an acute but severe noxious stimulus.

Expression of long-term potentiation in single wide dynamic range neurons in the rat is sensitive to blockade of glutamate receptors

Plasticity in pain control systems may play an important role in clinical pain and some mechanisms of plasticity may be similar to those involved in learning. In this study we investigate the importance of α-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) and N-methyl- d-aspartate (NMDA) receptors for the maintenance of long-term potentiation (LTP) in wide dynamic range (WDR) neurons. Doses of 6-nitro-7-sulphomoylbenzoylquinoxaline-2,3-dione disodium (NBQX) and D-Q-amino-5-phosphonopentanoic acid (D-AP5) equipotent in reducing C-fiber mediated responses in controls, reduced the established LTP by about 50 and 80%, respectively. The drug effect lasted less than 1 h in controls. After induction of LTP, NBQX caused a reversible reduction of the potentiation. D-AP5, however, caused a stronger attenuation of the LTP, outlasting the effect of the drug in controls. We suggest that both pre-emptive analgesia preventing LTP induction and an early reduction of the excitation of neurons is important for the inhibition of LTP and central sensitization. Thus, it is possible that an early antinociceptive treatment preventing an excessive excitation of neurons in the dorsal horn may be of importance in preventing long-lasting and pathological pain states.

LTP of spinal A beta and C-fibre evoked responses after electrical sciatic nerve stimulation.

Plasticity in the central nervous system may play an important role in clinical pain. The present study shows that long-term potentiation (LTP) may be induced in single wide dynamic range (WDR) neurons in the dorsal horn after high-frequency stimulation of the sciatic nerve in intact urethane anaesthetized rats. Extracellular recordings of firing responses after single pulse stimuli were made. The high-frequency conditioning stimulus increased the A beta- and C-fibre-mediated firing responses to single pulse stimuli by 60 and 130%, respectively, for more than 6 h. This finding supports a role for WDR neurons in 'nociceptive memory' in the dorsal horn. The model presented here may be an important tool for further investigations of mechanisms of plasticity within the dorsal horn.

Selective antagonism of capsaicin by capsazepine: evidence for a spinal receptor site in capsaicin‐induced antinociception

1. Capsazepine has recently been described as a competitive capsaicin antagonist. We have used this compound to test the hypotheses that the in vitro and in vivo effects of capsaicin are due to interactions with a specific receptor. 2. In an in vitro preparation of the neonatal rat spinal cord with functionally connected tail, the activation of nociceptive afferent fibres by the application of capsaicin, bradykinin or noxious heat (48 degrees C) to the tail could be measured by recording a depolarizing response from a spinal ventral root. Application of capsaicin or substance P to the spinal cord also evoked a depolarizing response which was recorded in a ventral root. 3. When capsazepine (50 nM-20 microM) was administered to the tail or spinal cord it did not evoke any measurable response. However on the tail, capsazepine reversibly antagonized (IC50 = 254 +/- 28 nM) the responses to capsaicin but not to heat or bradykinin administered to the same site. Similarly capsazepine administration to the spinal cord antagonized the responses evoked by capsaicin (IC50 = 230 +/- 20 nM) applied to the cord but not responses evoked by substance P on the cord or by noxious heat and capsaicin on the tail. 4. In halothane anaesthetized rats, C-fibre responses evoked by transcutaneous electrical stimulation of the receptive field were recorded from single wide dynamic range neurones located in the spinal dorsal horn. C-fibre evoked discharges were consistently reduced by the systemic administration of capsaicin (20 mumol kg-1, s.c.) and this action of capsaicin was antagonized by capsazepine (100 mumol kg-1) administered by the same route. In addition the systemic effect of capsaicin was antagonized by a spinal intrathecal administration of capsazepine (5-50 nmol). 5. Intradermal injections of capsaicin, localized to the peripheral receptive field, usually one toe of the ipsilateral hind-paw, produced a transient increase in C-fibre-evoked activity followed by a prolonged period of localized insensitivity to transcutaneous C-fibre stimulation. These effects of capsaicin were significantly reduced by the concommitant administration of capsazepine to the same site. 6. These data demonstrate that capsazepine is a selective antagonist of capsaicin on nociceptive neurones in vitro and in vivo and suggest that the effects of capsaicin were mediated by activation of a specific receptor. Since the antinociceptive effect produced by systemically administered capsaicin was antagonised by spinal intrathecal capsazepine this further supports the hypothesis that capsaicin exerts its antinociceptive effect by acting on specific receptors localized to sensory nerve fibres in the spinal cord.

δ receptor involvement in morphine suppression of noxiously evoked activity of spinal WDR neurons in cats

Morphine has been considered to be primarily a mu opiate receptor agonist. The present study was designed to determine if opiate receptor subtypes in addition to mu contribute to morphine analgesia at the level of the spinal cord. Extracellular activity of single wide dynamic range (WDR) neurons in the feline lumbar spinal cord were studied. Intrathecal administration of DAGO (selective mu agonist) or DPDPE (selective delta agonist) suppressed the noxiously (51 degrees C radiant heat) evoked activity of WDR neurons. Pretreatment with spinal beta-FNA (selective mu antagonist) antagonized the suppressive effects of spinal DAGO, but not that of DPDPE. Two doses of spinal morphine (200 and 400 micrograms) suppressed the noxiously evoked activity of WDR neurons confirming our previous report. Following beta-FNA pretreatment, the suppressive effects of morphine were reduced, however, when ICI 174,864 (selective delta antagonist) was co-administered with morphine on the spinal cord of the animals pretreated by beta-FNA, there was an even greater reduction in the neuronal suppression by morphine. Intravenous ICI 174,864 also reversed the suppressive effects of morphine in beta-FNA pretreated animals. beta-FNA antagonism of spinal morphine is evidence of the well-known mu receptor-mediating antinociception. However, antagonism by ICI 174,864 of morphine suppression in beta-FNA-pretreated animals demonstrates that morphine is capable of suppressing noxiously evoked activity of WDR neurons as a result of an interaction with delta receptors in addition to mu receptors at the level of spinal cord.

Antinociception produced by capsaicin: spinal or peripheral mechanism?

We have studied the effects of capsaicin, administered at concentrations found to be antinociceptive in behavioural tests, on nociceptive responses evoked both in spinal dorsal horn neurons in vivo and in spinal ventral roots in vitro. In halothane anesthetized rats, C-fibre evoked input produced by transcutaneous electrical stimulation in the peripheral receptive field was recorded from single wide dynamic range neurons located in superficial and deep dorsal horn of the lumbar spinal cord. This input was reduced by systemic administration of capsaicin at an antinociceptive dose (20 μmol/kg s.c.). Intradermal injections of capsaicin localized to the peripheral receptive field produced a transient increase in C-fibre evoked activity followed by a prolonged period of localized insensitivity to C-fibre stimulation. Spinal i.t. administered capsaicin also produced a rapid but reversible attenuation of peripherally evoked C-fibre input. In a neonatal rat spinal cord-tail preparation maintained in vitro, superfusion of the spinal cord with capsaicin (100–500 nM) produced a transient depolarization which was followed by an attenuation of responses to peripheral noxious heat and to spinal administration of substance P. Similar activity was produced by a prolonged superfusion of the spinal cord with substance P (50–200 nM). An HPLC method was used to estimate the concentration of capsaicin in a number of tissues following s.c. administration at an antinociceptive dose. In addition capsaicin concentrations were determined in the spinal cord following an i.t. administration. These data indicate that systematic doses of capsaicin, which are antinociceptive in behavioural tests, selectively attenuate C-fibre inputs to the dorsal horn. This effect is unlikely to be due to an inactivation of C-fibres at their peripheral locations but is more consistent with an action on the spinal cord in which desensitization to the effect of substance P, or other substances, released from primary afferent nerve terminals may play a prominant role.

The Antinociceptive Role of ??- and ??-Opiate Receptors and Their Interactions in the Spinal Dorsal Horn of Cats

This study was undertaken to examine the antinociceptive roles of different subtypes of opiate receptors and their interactions at the level of the spinal cord. We recorded extracellularly the activity of the single wide dynamic range neurons evoked by noxious radiant heat (51 degrees C) in decerebrate, spinally transected cats. The separate intrathecal administration of DAGO selective mu-agonist, n = 28), morphine (less selective mu-agonist, n = 22), DPDPE (selective delta-agonist, n = 25), and DADL (less selective delta-agonist, n = 17) produced statistically significant suppression of noxiously evoked activity in a time- and dose-dependent manner. In addition, intravenously administered naloxone (nonselective opiate antagonist) reversed the suppressive effects of all opiates studied. Intravenously administered ICI 174,864 (selective delta-antagonist) reversed the effects of DPDPE. These results, based on relative selectivity for opiate receptors, indicate that both mu- and delta-opiate receptors can modulate the input of nociceptive information in the spinal dorsal horn. To study interactions between mu- and delta-receptors at the level of the spinal cord, a combination of the above agonists was injected intrathecally--namely, an ineffective or slightly effective dose of DAGO (1 or 1.5 micrograms, respectively) that was combined with an ineffective dose of DPDPE (30 micrograms). The intrathecal combination of DAGO and DPDPE produced significant synergistic suppressive effects of noxiously evoked activity. These findings, again based on relative selectivity, suggest that drug combinations that include both selective mu- and delta-agonists may be a useful method of lowering the total amount of any one drug, thus decreasing the likelihood of side effects, while at the same time producing significant analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

C-primary afferent fibre mediated inhibitions in the dorsal horn of the decerebrate spinal rat : Exp. Brain Res., 51 (1983) 283–290

The effect of repetitive primary afferent C-fibre stimulation on the responses of single wide dynamic range neurones recorded in the dorsal horn of the spinal cord have been exaemined in the unanaesthetised decerebrate-spinal rat. Prolonged stimulation of the sural nerve at 0.5 Hz or higher produced both a progressive increase in the latency of the sural evoked C-responses in all units and a decrease or habituation of the number of C-evoked spikes in the majority of units (62%) recorded in laminae 5 and 6. The shift in latency of the C responses in the dorsal horn neurones was found to be the result of an activity-dependent reduction in the conduction velocity of the primary afferent C-fibres, but such stimulation did not decrease the size of the C compound action potential or produce a block in conduction of single polymodal C-fibres which could account for the habituation of the dorsal horn neurones. A complete habituation or failure of the C-evoked response in a dorsal horn neurone produced by repetitive stimulation of a peripheral nerve was associated with a reduction but not the abolishment of the convergent C-input from an adjacent untetanized nerve, indicating that the habituation did not occur as the result of a postsynaptic inhibition of the dorsal horn neurone. Following a C-tetanus (10 Hz for 10 s) applied to the sural nerve a short and partial homosynaptic post-tetanic inhibition of the subsequent C responses evoked from the sural occurs. Such sural nerve C-tetani however produced a much more powerful and prolonged heterosynaptic post-tetanic inhibition of the C-responses evoked from the common peroneal nerve in those units with convergent C-input from both these two adjacent nerves. None of the effects of repetitive peripheral C-fibre stimulation on the C-evoked responses in the dorsal horn could be produced by A-fibre conditioning stimuli applied at identical frequencies. These results indicate that there is a segmentally organized C afferent-mediated inhibition of C-evoked responses in dorsal horn neurones that is generated both by the C-input that evoked those responses and by adjacent C-inputs.

C-primary afferent fibre mediated inhibitions in the dorsal horn of the decerebrate-spinal rat

The effect of repetitive primary afferent C-fibre stimulation on the responses of single wide dynamic range neurones recorded in the dorsal horn of the spinal cord have been exaemined in the unanaesthetised decerebrate-spinal rat. Prolonged stimulation of the sural nerve at 0.5 Hz or higher produced both a progressive increase in the latency of the sural evoked C-responses in all units and a decrease or habituation of the number of C-evoked spikes in the majority of units (62%) recorded in laminae 5 and 6. The shift in latency of the C responses in the dorsal horn neurones was found to be the result of an activity-dependent reduction in the conduction velocity of the primary afferent C-fibres, but such stimulation did not decrease the size of the C compound action potential or produce a block in conduction of single polymodal C-fibres which could account for the habituation of the dorsal horn neurones. A complete habituation or failure of the C-evoked response in a dorsal horn neurone produced by repetitive stimulation of a peripheral nerve was associated with a reduction but not the abolishment of the convergent C-input from an adjacent untetanized nerve, indicating that the habituation did not occur as the result of a postsynaptic inhibition of the dorsal horn neurone. Following a C-tetanus (10 Hz for 10 s) applied to the sural nerve a short and partial homosynaptic post-tetanic inhibition of the subsequent C responses evoked from the sural occurs. Such sural nerve C-tetani however produced a much more powerful and prolonged heterosynaptic post-tetanic inhibition of the C-responses evoked from the common peroneal nerve in those units with convergent C-input from both these two adjacent nerves. None of the effects of repetitive peripheral C-fibre stimulation on the C-evoked responses in the dorsal horn could be produced by A-fibre conditioning stimuli applied at identical frequencies. These results indicate that there is a segmentally organized C afferent-mediated inhibition of C-evoked responses in dorsal horn neurones that is generated both by the C-input that evoked those responses and by adjacent C-inputs.