Non-noxious Cutaneous Stimuli Research Articles

Pain when walking: individual sensory profiles in the foot soles of torture victims - a controlled study using quantitative sensory testing.

BackgroundWith quantitative sensory testing (QST) we recently found no differences in sensory function of the foot soles between groups of torture victims with or without exposure to falanga (beatings under the feet). Compared to matched controls the torture victims had hyperalgesia to deep mechano-nociceptive stimuli and hypoesthesia to non-noxious cutaneous stimuli. The purpose of the present paper was to extend the group analysis into individual sensory profiles of victims’ feet to explore possible relations between external violence (torture), reported pain, sensory symptoms and QST data to help clarify the underlying mechanisms.MethodsWe employed interviews and assessments of the pain and sensory symptoms and QST by investigators blinded to whether the patients, 32 male torture victims from the Middle East, had (n=15), or had not (n=17) been exposed to falanga. Pain intensity, area and stimulus dependence were used to characterize the pain. QST included thresholds for touch, cold, warmth, cold-pain, heat-pain, deep pressure pain and wind-up to cutaneous noxious stimuli. An ethnically matched control group was available.The normality criterion, from our control group data, was set as the mean +/− 1.28SD, thus including 80% of all values.QST data were transformed into three categories in relation to our normality range; hypoesthesia, normoesthesia or hyperesthesia/hyperalgesia.ResultsMost patients, irrespective of having been exposed to falanga or not, reported severe pain when walking. This was often associated with hyperalgesia to deep mechanical pressure. Hypoesthesia to mechanical stimuli co-occurred with numbness, burning and with deep mechanical hyperalgesia more often than not, but otherwise, a hypoesthesia to cutaneous sensory modalities did not co-occur systematically to falanga, pain or sensory symptoms.ConclusionIn torture victims, there seem to be overriding mechanisms, manifested by hyperalgesia to pressure pain, which is usually considered a sign of centralization. In addition there was cutaneous hypoesthesia, but since there was no obvious correlation to the localization of trauma, these findings may indicate centrally evoked disturbances in sensory transmission, that is, central inhibition. We interpret these findings as a sign of changes in central sensory processing as the unifying pathological mechanism of chronic pain in these persons.

Effectiveness of riluzole in suppressing spasticity in the spinal cord injured rat

Spasticity poses a major detrimental impact on the quality of life in a significant number of people with spinal cord injury (SCI). Recent observations in our laboratory suggest that spinal transection at the sacral S 2 level induces a significant increase in glutamatergic input to sacrocaudal motoneurons during the time spasticity is present in the tail muscles. The present study examined the effectiveness of riluzole, an agent that has been shown to reduce glutamate release, in managing spasticity within the tail musculature. In this blinded, cross-over study animals with S 2 spinal transections were tested behaviorally for the progression of spasticity in the tail musculature using our established system. When the animals demonstrated a significant level of spastic behavior (e.g. increased response to quick stretch, noxious and non-noxious cutaneous stimuli), they received either saline or riluzole (8 or 10 mg/kg i.p.) and assessed behaviorally at 1, 3, 6, and 12 post-injection. Results: riluzole at 8 mg/kg significantly decreased the response of the tail muscle to noxious and non-noxious cutaneous stimuli for the first 3 h post-administration, while administration of riluzole at 10 mg/kg significantly decreased the responsiveness of the tail to all of the behavioral assessments. However, a significant percentage of the animals displayed motor impairments at this higher dosage. Conclusion: suppression of glutamate release by the administration of riluzole can reduce several, but not all, aspects of spastic activity in the tail muscles at concentrations that do not elicit negative side-effects.

Gabapentin suppresses spasticity in the spinal cord–injured rat

Spasticity poses a major detrimental impact on the quality of life in a significant number of people with spinal cord injury (SCI). Recent observations in our laboratory suggest that spinal transection at the sacral S 2 level induces a significant increase in glutamatergic input to sacrocaudal motoneurons during the time spasticity is present in the tail muscles. The present study examined the efficacy of gabapentin, an agent that has been shown to reduce glutamate release, in managing spasticity within the tail musculature. Method In this blinded, crossover study adult Sprague-Dawley rats with S 2 spinal transections were tested behaviorally for the progression of spasticity in the tail musculature using our established system. When the animals demonstrated a significant level of spastic behavior (e.g. increased response to quick stretch, noxious and non-noxious cutaneous stimuli), they received either saline or the antiepileptic agent gabapentin (GBP; 50 mg/kg i.p.) and were assessed behaviorally and electrophysiologically at 1, 3, 6, 12 and 24 h post-injection. Results Both spastic behavior and electromyography (EMG) activity were significantly decreased at 1 and 3 h post-GBP injection when compared with the activity level following administration of saline. Spastic behavior and EMG activity gradually increased over time and returned to baseline activity by 24 h post-injection. Conclusion Gabapentin diminishes both the behavioral and electrophysiological manifestation of SCI-induced spasticity, in the tail musculature, in a time dependent manner.

Which Spinal Cutaneous Nociceptive Neurons Are Inhibited by Intravenous Lidocaine in the Rat?

Intravenous lidocaine (IVL) produces analgesia in multiple painful disorders. The neurophysiological effects of IVL are not well defined, but studies in visceral nociceptive systems have shown that IVL has differential effects on subgroups of spinal neurons. The present study determined whether a similar differential effect of IVL occurs in spinal neurons excited by noxious cutaneous stimuli. In decerebrate, cervical spinal cord-transected rats, the lumbosacral spinal cord was exposed by a laminectomy. Single-unit recordings were made of dorsal horn neurons excited by noxious cutaneous stimuli. Each neuron's response to noxious (pinch) and nonnoxious (brush) cutaneous stimuli were determined and the effect of a counterirritation stimulus (noxious skin pinch presented in the upper body) on spontaneous activity quantified. In a subset of neurons, sequential doses of IVL were administered, and responses of each neuron to repeated 50 degrees C heating of the hindpaw/tail were determined. IVL dose-dependently inhibited neurons excited by heating of the hindpaw/tail. IVL produced significantly greater inhibition of both spontaneous and heat-evoked activity in neurons that did not show counterirritation effects when compared with those neurons that did show counterirritation effects. Standard classification of neurons as wide-dynamic range or nociceptive-specific was less predictive of the IVL effect. IVL had differential inhibitory effects on 2 spinal cutaneous nociceptive neuron populations. Other drugs could also have differential effects on sensory pathways, suggesting a mechanism whereby certain drugs differentially affect different types of pain.

Spinal neurophysiologic correlates of the analgesic actions of intravesical dimethyl sulfoxide and capsaicin in the rat

Peripheral analgesia produced by the intravesical instillation of dimethyl sulphoxide (DMSO) and capsaicin has been used to treat visceral pain originating in the urinary bladder. The present study sought to determine the neurophysiologic consequences of the intravesical instillation of these compounds by measuring spinal neuronal responses evoked by urinary bladder distension (UBD) in the rat. Subjects were spinally transected, decerebrate female Sprague-Dawley rats. The effect of 0.5 mL of solution of 10% or 50% DMSO, 100 μmol/L capsaicin, or the same volume of saline instilled into the bladder on excitatory neuronal responses to UBD was studied by using single-unit extracellular recordings of L6-S2 dorsal horn spinal cord neurons. Fifty-six dorsal horn neurons that were excited by UBD in a graded fashion were identified. All neurons were also excited by noxious or non-noxious cutaneous stimuli. Two hours after intravesical instillation, solutions of 50% DMSO or 100 μmol/L of capsaicin produced a reduction of the slope of stimulus-response functions for neuronal activity evoked by graded UBD. These data support a local effect of intravesical 50% DMSO or capsaicin and suggest the use of this model to study novel peripheral treatment strategies for bladder pain. © 2002 by the American Pain Society

Ketamine, an N-methyl-D-aspartate receptor antagonist, inhibits the spinal neuronal responses to distension of the rat urinary bladder.

The effect of ketamine as a treatment of visceral pain is not known. The current study investigated the effect of ketamine on spinal dorsal horn neurons excited by urinary bladder distension (UBD). The effect of other clinically available N-methyl-D-aspartate receptor antagonists on these responses was also studied. Extracellular recordings of neurons located in the L6-S2 spinal dorsal horn of cervical spinal cord-transected, decerebrate female rats were obtained. Cutaneous receptive fields of neuronal units excited by UBD were characterized for responses to segmental noxious and nonnoxious stimuli. Nonsegmental noxious stimuli were also applied, and neurons were classified as type I (inhibited) and type II (noninhibited) by the stimulus. The effect of intravenous ketamine (1, 3, and 10 mg/kg), dextromethorphan (5 mg/kg), and memantine (16 mg/kg) on neuronal responses of these units was measured. Spontaneous and evoked neuronal activity to UBD was reduced in a dose-dependent fashion by ketamine. Responses to nonnoxious cutaneous stimuli were also significantly reduced after treatment. Dextromethorphan inhibited neuronal activity evoked by UBD in type I neurons. A similar selective effect of treatment on type I versus type II neurons was observed after intravenous ketamine and memantine. Intravenous ketamine produces dose-dependent inhibition of the spinal cord neuronal responses evoked by UBD. All three N-methyl-D-aspartate receptor antagonists showed selective effects on spinal cord neurons subject to counterirritation. This neurophysiologic evidence supports a spinally mediated analgesic effect of ketamine in this model of urinary bladder nociception, an effect likely caused by N-methyl-D-aspartate receptor antagonism.

Effects of electrical stimulation of thalamic nucleus submedius and periaqueductal gray on the visceral nociceptive responses of spinal dorsal horn neurons in the rat

Electrical stimulation of the nucleus submedius (Sm) has been shown to suppress the viscerosomatic reflex (VSR), which is evoked by colorectal distension (CRD). We have examined the effects of focal electrical stimulation (0.3 ms, 50 Hz, 100 μA, 10 s) of the Sm and the periaqueductal gray (PAG) on the excitatory responses evoked by CRD in spinal dorsal horn neurons within the L6–S1 region in the urethane-anesthetized Wistar rats. Extracellular recordings were made from 32 spinal excitatory CRD responses. All of these neurons were convergent neurons with cutaneous receptive fields. The majority of the neurons (27/32) were wide dynamic range (WDR) neurons (responding to noxious and non-noxious cutaneous stimuli) while the remaining five neurons were nociceptive specific (NS) neurons (responding only to noxious cutaneous stimuli). The effects of electrical stimulation applied to 28 sites within the Sm were assessed for spinal neurons. Electrical stimulation in seven sites within the Sm (25%) inhibited the CRD excitatory response of dorsal horn neurons, while in two sites (7%) the same stimulation yielded facilitation. Electrical stimulation in the majority of the sites in the Sm (19/28, 68%) did not affect spinal excitatory CRD responses. On the other hand, electrical stimulation of the PAG clearly inhibited 20 of 22 (90%) CRD excitatory responses. These results suggest that the majority of Sm neurons may suppress VSR activity at a supraspinal reflex center rather than via a descending inhibition of spinal visceral nociceptive transmission, as is the case for the PAG.

The effect of morphine on responses of mediodorsal thalamic nuclei and nucleus submedius neurons to colorectal distension in the rat

In halothane-anesthetized rats, we characterized the responses of single neurons in the nuclei of medial thalamus (MT), specifically the mediodorsal thalamic nucleus (MD) and the nucleus submedius (Sm), to a noxious visceral stimulus (colorectal balloon distension, CRD), and studied the effects of intravenous morphine (Mor) on these responses using standard extracellular microelectrode recording techniques. 62 MD and 46 Sm neurons were isolated on the basis of spontaneous activity. 47 of the MD neurons (76%) responded to CRD, of which 70% had excitatory and 30% had inhibitory responses. 38 of the Sm neurons (83%) responded to CRD, of which 89% had excitatory and 11% had inhibitory responses. Responses of MD and Sm neurons excited by CRD were related significantly to distension pressure (20–100 mmHg), with maximum excitation occurring at 60 and 100 mmHg, respectively. MD neurons inhibited by CRD also had graded responses to graded CRD, with maximum inhibition occurring at 80 mmHg. The responses to noxious (pinch, heat) and nonnoxious (tap, brush) cutaneous stimuli were studied in 59 of the MD and 44 of the Sm neurons isolated. 22 of the MD neurons (37%) studied had cutaneous receptive fields, of which 59% were large and bilateral, 41% were small and usually contralateral receptive fields. 55% of these neurons were nociceptive-specific, 45% responded to both noxious and nonnoxious cutaneous stimulation. 29 of the Sm neurons (66%) studied had cutaneous receptive fields, of which 72% were large and usually bilateral, 14% were small and bilateral, 14% were small and contralateral receptive fields. 90% of these neurons were nociceptive-specific, 10% responded to both noxious and nonnoxious stimulation. No MD or Sm neurons responded exclusively to nonnoxious cutaneous stimulation. Mor (0.125, 0.25, 0.5 and 1 mg/kg IV) attenuated MD and Sm neuronal excitatory responses to CRD in a dose-dependent fashion, abolishing evoked activity with a dose of 0.5 mg/kg ( p<0.05) and 1 mg/kg ( p<0.05), respectively. Naloxone (0.4 mg/kg IV) reversed the effects of Mor. Mor and naloxone had no effects on spontaneous activity. These data support the involvement of MD and Sm neurons in visceral nociception, and are consistent with a role of Sm in affective-motivational, and MD in both sensory-discriminative and affective-motivational aspects of nociception.

Antagonism of nociceptive responses of cat spinal dorsal horn neurons in vivo by the NK-1 receptor antagonists CP-96,345 and CP-99,994, but not by CP-96,344.

Extracellular and intracellular studies were undertaken to test the effects of the non-peptide, substance P (NK-1) receptor antagonists CP-96,345 and CP-99,994, and of CP-96,344, the inactive enantiomer of CP-96,345, on the responses of spinal dorsal horn neurons to peripheral noxious and non-noxious cutaneous stimuli in spinalized cats anesthetized with alpha-chloralose. The effect of these agents on the response of dorsal horn neurons to iontophoretic application of substance P was also tested in extracellular studies. The substance P-induced slow, prolonged discharge of dorsal horn neurons was blocked by administration (0.5 mg/kg, i.v.) of CP-96,345 (n = 10) or CP-99,994 (n = 9), but was unaffected by CP-96,344 (n = 9). The response of substance P-sensitive neurons to noxious thermal stimulation of the cutaneous receptive field, especially the late afterdischarge phase, was also significantly inhibited by CP-96,345 (n = 10) and by CP-99,994 (n = 7). The response of such neurons to noxious pinch stimulation of the receptive field was also significantly inhibited by CP-96,345 (n = 7) and CP-99,994 (n = 8), but the response of three other substance P-sensitive neurons to pinch was unaffected by CP-96,345. CP-96,344 did not affect the response of any neuron tested to either of these noxious stimuli (noxious thermal, n = 7; pinch, n = 6). The response to hair afferent stimulation was unaffected by any of these compounds (CP-96,345, n = 16; CP-96,344, n = 5; CP-99,994, n = 6). In intracellular studies, the effect of these antagonists was tested on responses of dorsal horn neurons to noxious pinch stimulation or to a train of high intensity electrical stimulation of the superficial peroneal nerve. Both stimuli produced an initial fast depolarization followed by a slow and prolonged depolarization with corresponding discharge patterns. CP-96,345 (n = 3) and CP-99,994 (n = 6) selectively blocked the late, slow components of the stimulus-evoked response without affecting the early components. Responses to single electrical pulses of the same intensity and duration were not affected. CP-96,344 did not affect any of the responses tested (n = 5). The data indicate that nociceptive responses of a subset of spinal dorsal horn cells are selectively blocked by the NK-1 receptor antagonists, CP-96,345 and CP-99,994, thus confirming the involvement of NK-1 receptors in these responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthetic blockade of the dorsolateral funiculus enhances evoked activity of spinal cord dorsal horn neurons.

1. A previous study of cat lumbar dorsal horn neurons found reduced responsiveness to A-fiber stimulation 1.5-12 h after thoracic dorsolateral funiculus (DLF) lesions. The present study was undertaken to determine whether this was due to the loss of descending activity or to factors specifically associated with injury by examining the response properties of dorsal horn cells before and during lidocaine blockade of the ipsilateral DLF. Electric shocks applied to the dorsal columns were used to search for dorsal horn cells. Noxious and nonnoxious cutaneous mechanical stimuli and graded electrical stimuli applied to the tibial nerve were used to activate peripheral afferent fibers. Cells were classed as low threshold (LT), high threshold (HT), or multireceptive (MR), according to their responses to natural stimuli. Baseline data were collected from a total of 58 cells. Twelve of these were further studied after lidocaine injection of the DLF. All cells examined with lidocaine were in dorsal horn laminae III-V. 2. All cells responded to activation of tibial nerve A fibers. However, the median threshold for the HT and MR cells (200 microA) was significantly higher than that of the LT cells (75 microA). Some cells in each class were also activated by C fibers (10, 70, and 64% of the LT, HT, and MR cells, respectively). 3. For the cells that were further characterized by lidocaine blockade of the DLF, all LT cells (n = 3) responded only to A-fiber stimulation, and all HT (n = 3) and MR cells (n = 6) responded to both A- and C-fiber stimulation. 4. For LT cells, responses evoked by mechanical and electrical stimuli were unaltered by lidocaine blockade. 5. HT and MR cells showed enhanced responses to electrical stimulation of C fibers during DLF blockade. There was no consistent effect of the blockade on A-fiber-evoked responses. 6. Two of three HT and four of six MR cells studied with lidocaine had spontaneous activity, which exhibited a small but significant increase during DLF blockade. 7. Receptive fields for noxious stimulation expanded in two of six MR cells during DLF blockade. Two of three HT cells developed responses to tactile stimuli during the blockade. 8. In two additional cells (1 HT and 1 MR), spontaneous activity and responses to C-fiber input increased after the DLF was cut.(ABSTRACT TRUNCATED AT 400 WORDS)

Lack of interaction between methionine enkephalin and d-phenylalanine on nociceptive and non-nociceptive responses of dorsal horn neurones of the cat

In the spinal cord of the barbiturate anaesthetized cat, D-phenylalanine (DPA) depressed spontaneous and amino acid-induced firing of multireceptive dorsal horn neurones. The excitation of these neurons by noxious and non-noxious cutaneous stimuli was non-selectively depressed by DPA. DPA did not potentiate the depressant action of methionine enkephalin on these cells. Although naloxone reduced the depressant action of DPA, this was associated with increases in spontaneous firing. Spinal reflexes in this preparation are tonically inhibited by opioid peptides. Intravenous DPA (20–70 mg/kg) did not potentiate this inhibition but produced small increases in spinal reflexes. Collectively these data do not support the hypothesis that analgesia from DPA results from potentiation of endogenously released methionine enkephalin.

Do convergent neurones in the spinal dorsal horn discriminate nociceptive from non-nociceptive information?

Thirty convergent neurones responding to both noxious and non-noxious cutaneous stimuli were recorded at the lumbar level in either anaesthetized ‘intact’ rats or unanaesthetized ‘spinal’ rats. Their responses to radiant heat application and to repetitive innocuous mechanical stimulation of the centre of their receptive fields were analysed, both in terms of the maximal and the mean firing rates. These neurones increased their discharge rates in relation to the temperature applied to their receptive fields with the highest levels being produced by noxious intensities. This finding confirms earlier reports suggesting the capacity of these neurones to encode nociceptive information of thermal origin. However, a very high level of firing could also be evoked by repetitively applied innocuous mechanical stimuli. This was a consistent finding, observed both in intact and spinal animals, which was true for the two subgroups into which we divided the convergent neurones (warming/noxious heat units and noxious heat units). These results are discussed in terms of the role of convergent neurones in nociception. It is suggested that a single channelled signal emanating from these neurones could not be the basis of a clear nociceptive message to the brain; two alternative hypotheses involving multichannelled organizations of impulses are proposed for discussion.

Tolerance and dependence of dorsal horn neurones of the cat: The role of the opiate receptors of the substantia gelatinosa

The effects of morphine and of naloxone were examined on dorsal horn neurones of pentobarbitone-anaesthetized spinal cats pretreated twice daily for 3 days with increasing doses of morphine hydrochloride (2–20 mg/kg). Action potentials of neurones in laminae IV in segments L 5-L 7 were recorded extracellularly. Neurones were activated by noxious and non-noxious cutaneous stimuli, or by electrical stimulation of unmyelinated primary afferents in the tibial nerve. These responses were not depressed by doses of morphine 10–200 times greater than those producing depressant effects on neurones from untreated cats. Electrophoretic administration of naloxone in the substantia gelatinosa caused marked increases in the responses. To assess tolerance and dependence, the noxious skin temperature producing half the maximum increase in the number of spikes evoked (the T 50) was determined from skin temperature-response curves. The mean T 50 's for neurones from untreated (48.8 C) and from morphine-treated cats (47.7 C) were not significantly different, suggesting tolerance to the normal depressant effect of morphine. Electrophoretic administration of naloxone in the substantia gelatinosa produced a selective increase in the response to noxious heat, and a significant reduction in the mean T 50 (45.5 C), indicating withdrawal hyperexcitability. The experiments suggest that opiate receptors of the substantia gelatinosa may be important in signs of tolerance and dependence.

Functional changes in ventrobasal thalamic neurones responsive to noxious and non-noxious cutaneous stimuli after chloralose treatment: New evidence for the presence of pre-existing “silent connections” in the adult nervous system?

Twenty-five neurones of the thalamic VB complex of the rat, first characterized under moderate volatile anaesthesia ( 1 3 oxygen− 2 3 nitrous oxide , 0.5% halothane) were subsequently studied under deep chloralose anaesthesia. As described in a previous study, neurones were classified during the control period as “noxious” (N), “non-noxious” (Nn), or “convergent” (NnN) according to their responsiveness to cutaneous mechanical stimulations. For all the N (n = 15) and NnN (n = 4) neurones, the responses induced by noxious stimuli (mechanical electrical or thermal) progressively disappeared after chloralose administration. Simultaneous with disappearance of the responses elicited by noxious stimuli, responses to non-noxious stimuli appeared for 12 N neurones: 5 responded to a brisk tap applied to any part of the body, and 7 to brushing of light touch from a new receptive field (RF), at a variable distance from the initial RF, but always contralateral to the recording site. The Nn neurones (n = 6) continued to be activated by light touch or brushing but there was a consistent concentric enlargement of their RF. The NnN neurones also presented an enlarged RF to the non-noxious stimuli. The depressive and “unmasking” effects of chloralose are discussed and compared to the various indications of pre-existing connections in the CNS.

Posterior intralaminar region in rat: Neuronal responses to noxious and nonnoxious cutaneous stimuli

We recorded from 125 neurons affected by noxious and nonnoxious cutaneous stimuli in the thalamic posterior intralaminar region (PIR) in rats anesthetized with a mixture of 2 3 N 2O - 1 3 O 2 and 0.5% halothane. Twenty-seven neurons were exclusively excited by a nonoxious brisk tap sharply applied on any part of the body. Ninety-eight neurons were affected by noxious stimuli, 25 being inhibited and 73 activated. In addition, 34 98 were also excited by tapping. Noxious stimuli were efficacious whatever their location on the body surface. The different kinds of cells seemed to be intermingled in the PIR; however, “tap” and “noxious activated” neurons were less numerous in the rostrodorsal than in the other sectors. Neurons excited by noxious cutaneous stimuli were also tested with intense transcutaneous electrical stimulation. They exhibited an easily reproducible bursting response whose latency (20 to 40 ms) was consistent with an Aδ fiber input. Fifteen noxious activated neurons were tested with graded noxious heat. Response thresholds were high (48.9 ± 1.37°C); no unit was observed which encoded stimulus temperature by frequency of discharge, moreover, there was a great variability of responses to an identical stimulus. All these data indicate that PIR neuronal responses to noxious stimuli largely differ from those of the ventrobasal complex of the thalamus and play an eventual role in nociception processes.

Neuronal responses to cutaneous electrical and noxious mechanical stimuli in the nucleus reticularis thalami of the rat

Responses of 81 neurons accurately localized in the nucleus reticularis thalami (RT) of moderately anesthesized rats were tested for response to noxious and non-noxious cutaneous stimuli. Spontaneous firing rates were very high (between 18 and 60 Hz) and regular. Non-noxious stimuli did not modify the activity of RT neurons. By contrast, in 62 81 RT neurons, noxious cutaneous mechanical stimuli induced a strong and short-latency depression of firing, irrespective of the location of the stimulus on the body surface. Intense (> 3 mA) transcutaneous electrical stimulation also elicited long-lasting depressions of the firing in most cases. The hypothesis of a possible role of the RT nucleus in inhibitory controls exerted upon noxious messages relayed in the thalamic ventrobasal nucleus is discussed.

Neurones responding to noxious stimulation in VB complex and caudal adjacent regions in the thalamus of the rat

1. (1) 163 cells responding to mechanical cutaneous stimulation have been recorded in VB complex and caudal adjacent region in rats anaesthetized with a mixture of 2 3 N 2 O− sol1 3 O 2 and 0.5% halothane. 2. (2) 51 cells were exclusively activated by non-noxious cutaneous stimuli applied to restricted and contralateral receptive fields (RF) and had the classical characteristics of “lemniscal” responses. 93 cells responded only to noxious mechanical stimuli (N cells) and had either uni- or bilateral receptive fields. 19 cells responded both to noxious and non-noxious stimuli (NnN cells). 3. (3) When tested with intense electrical stimuli applied transcutaneously or on the sural nerve, N and NnN cells responded with a late irregular discharge. Poststimulus histograms obtained in one-third of these units revealed that the late component was consistent with a C fibre input; some of responses were consistent with Aδ fibre input. NnN cells also had a short latency discharge probably due to Aδ fibre involvement. 4. (4) When tested with other intense stimuli such as noxious radiant heat or noxious visceral stimulation induced by intraperitoneal injection of bradykinin, N and NnN cells were strongly activated. 5. (5) The different kinds of cells were scattered in VB and PO and no significant differences were found between cells recorded in VB and caudal adjacent region (PO); however, a rostrocaudal organization of the cells, according to the location of their RF on the caudal or rostral part of the body, was clear not only for the Nn cells but also for N and NnN cells.

Lack of effect by substance P at sites in the substantia gelatinosa where met-enkephalin reduces the transmission of nociceptive impulses

In α-chloralose anaesthetized spinal cats, Met-enkephalin amide (M-ENKA) and substance P were administered electrophoretically in the substantia gelatinosa while studying the excitation of deeper spinal neurones by noxious and non-noxious cutaneous stimuli. At sites where Met-enkephalin selectively reduced excitation by noxious skin stimuli, substance P was without effect. This result does not support the hypothesis that enkephalins are released at axo-axonic synapses on the terminals of substance P releasing primary afferent fibres.

Inhibition of the spinal transmission of nociceptive information by supraspinal stimulation in the cat

In cats anaesthetized with α-chloralose or sodium pentobarbitone a study was made of the effects of supraspinal electrical stimulation on the excitation of dorsal horn neurones by noxious and non-noxious cutaneous stimuli. Stimulation near the dorsal raphe of the midbrain non-selectively reduced the responses of neurones to both noxious and non-noxious stimuli. Intravenous naloxone (0.3–0.6 mg/kg) had no effect on this inhibition. Electrical stimulation near the medullary raphe selectively reduced the excitation of dorsal horn neurones by noxious cutaneous stimuli. Excitation of neurones by deflection of hairs was unaffected. The inhibition of nociceptive responses outlasted the period of raphe stimulation by up to 6 min. Intravenous naloxone (0.6–1.0 mg/kg) also failed to affect this selective inhibition.

The effect of naloxone on the excitation of dorsal horn neurones of the cat by noxious and non-noxious cutaneous stimuli

The effect of naloxone on the excitation of dorsal horn neurones of the cat by noxious and non-noxious cutaneous stimuli