C-fiber Activation Research Articles

Somatosensory inhibition of vagal baroreflex bradycardia: afferent nervous mechanisms.

Sensory receptors, afferent fibers, and spinal ascending pathways involved in somatosensory inhibition of baroreflex vagal bradycardia (BVB) were studied in chloralose-urethan-anesthetized rats. BVB was induced by electrical stimulation of the aortic depressor nerve (ADN). Among mechanical and thermal stimuli applied on a hindlimb, hot water (55 degrees C) immersion was most effective to inhibit BVB. Static hindlimb muscle contraction by ventral root stimulation also produced BVB inhibition that was abolished by muscle relaxation. These findings suggest that thermal nociceptors and muscle receptors, probably chemoreceptors, trigger BVB inhibition when activated. Furthermore, afferent fiber groups responsible for BVB inhibition due to sciatic nerve (ScN) or sural nerve (SU) stimulation were determined. BVB was largely inhibited by activation of A delta-fibers of the ScN or SU, but C-fiber contribution to BVB inhibition was also ascertained by means of selective C-fiber activation. Finally, courses of spinal pathways mediating ScN inhibition of BVB were localized as follows. First, ADN-vagal baroreflex arc of one side was interrupted by unilateral vagotomy. Then ScN inhibition of BVB provoked by the remaining reflex arc was analyzed after spinal cord hemisection at C1 and subsequent lesioning of the cord on the nonsectioned side. Regardless of whether the spinal cord was hemisectioned on any side with respect to the target reflex arc, stimulation of the ScN of either side still inhibited BVB, unless the lateral funiculus of nonsectioned side was extensively lesioned. In conclusion, the spinal BVB-inhibitory pathways are multifold, projecting to bilateral baroreflex vagal centers by crossing the midline at spinal or/and medullary levels.

Effects of chemical and electrical stimulation of the midbrain on feline T 2-T 6 spinoreticular and spinal cell activity evoked by cardiopulmonary afferent input

Responses to electrical and chemical stimulation of the periaqueductal gray (PAG) and midbrain reticular formation (RF) were examined on extracellular activity of 28 spinoreticular tract (SRT) and 56 spinal neurons in T 2–T 6 segments of anesthetized cats. All cells received excitatory viscerosomatic convergent input from the left forelimb triceps region and from cardiopulmonary sympathetic afferents. Evoked activity that resulted from pinching the left triceps was reduced by PAG and midbrain RF stimulation (100 Hz, 100 μs, 50–500 μA). Visceral afferent input to the neurons was elicited during electrical stimulation of the PAG and adjacent RF decreased A-δ and C-fiber activation of these neurons produced during electrical stimulation of cardiopulmonary afferents and decreased the activity of cells during excitatory responses to intracardiac bradykinin. Electrical stimulation of the PAG or midbrain RF similarly decreased spontaneous and evoked cell activity. Selective activation of cell bodies with microinjection of glutamate into the PAG reduced the activity of 6 to 8 cells whereas glutamate injections into midbrain RF reduced the activity of only 3 of 13 neurons. This difference in the effectiveness of chemically stimulating the PAG vs midbrain RF was significant (P < 0.05). These data demonstrate that (1) neuronal activity evoked by visceral afferent input from the heart was decreased by electrical stimulation of the PAG and midbrain RF and (2) a portion of this descending inhibition may be mediated by cell bodies in the PAG.

Intracerebroventricular morphine decreases descending inhibitions acting on lumbar dorsal horn neuronal activities related to pain in the rat : D. Bouhassira, L. Villanueva and D. Le Bars, J. Pharmacol. Exp. Ther., 247 (1988) 332–342

Recordings were made from convergent neurons in the lumbar dorsal horn of the rat. These neurons were activated by both innocuous and noxious stimuli applied to their excitatory receptive fields located on the extremity of the ipsilateral hindpaw. Transcutaneous application of suprathreshold 2-msec square-wave pulses to the center of the receptive field resulted in responses to A- and C-fiber activation being observed: 27.2 +/- 2.2 (mean +/- S.E.M.) C-fiber latency spikes were evoked per stimulus. This type of response was inhibited by applying noxious conditioning stimuli to heterotopic areas of the body; in particular, immersing the tail in a 52 degrees C waterbath caused a 74.2 +/- 2.0% inhibition of the C-fiber evoked responses; such inhibitory processes have been termed diffuse noxious inhibitory controls (DNIC). The effects of microinjections of morphine (0.6-40 micrograms; 2 microliter) within the 3rd ventricle on both the unconditioned C-fiber-evoked responses and the inhibitory processes triggered from the tail were investigated in an attempt to answer two questions: 1) does i.c.v. morphine increase tonic descending inhibitory processes? and 2) what are the effects of i.c.v. morphine on descending inhibitory processes triggered phasically by noxious stimuli? The predominant effect of i.c.v. morphine on the C-fiber-evoked responses was a facilitation (17 of 26 cases). Such a facilitation was dose-related in the 0.6 to 40 microgram range and naloxone reversible; it plateaued from 20 min after the microinjection. No clear relationship was found between the number of C-fiber evoked responses in the control sequences and the subsequent effect of i.c.v. morphine. Intracerebroventricular morphine clearly reduced DNIC in the majority of cases (21 of 26). Such a reduction was dose-related in the 0.6 to 2.5 microgram range and naloxone reversible; it plateaued within 90 min of microinjection. No clear relationship was found between the changes in DNIC and either the number of C-fiber-evoked spikes in the control sequences or the changes in the C-fiber responses induced by i.c.v. morphine. Autoradiographic controls using [3H]morphine showed a labeling along the ventricle wall including the hypothalamus, the periaqueductal gray matter and the floor of the 4th ventricle, three regions which have been implicated in the control of nociceptive transmission at the spinal level. Diffusion from the ventricle wall was over a distance of 0.5 mm and was identical whether observed 20 or 95 min after the microinjections.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrophysiological characteristics of primate spinothalamic neurons with renal and somatic inputs.

1. Spinothalamic tract (STT) neurons in the T10-L3 segments were studied for responses to renal and somatic stimuli. A total of 90 neurons was studied in 25 alpha-chloralose anesthetized monkeys (Macaca fascicularis). All neurons were antidromically activated from the ventral posterior lateral nucleus of the thalamus. 2. Sixty-two cells were excited by renal nerve stimulation and six inhibited. Probability of locating cells with renal input was greatest in T11-L1. Cells were located in laminae I and IV-VII; however, most were located in laminae V-VII. Antidromic latencies averaged 4.61 +/- 0.32 (SE) ms, whereas antidromic conduction velocities averaged 43.23 +/- 9.03 m/s. 3. Cells with excitatory renal input received A delta input only (36 cells) or A delta- and C-fiber inputs (26 cells). Stimulation of A delta renal afferent fibers evoked bursts of 1-10 spikes/stimulus [mean 3.6 +/- 0.9 spikes/stimulus] with onset latencies of 10.7 +/- 0.5 ms. Stimulation of C-fibers evoked 1.3 +/- 0.5 spikes/stimulus with onset latencies of 61.7 +/- 11.1 ms. Magnitude of responses to A delta-fiber stimulation was greatest in T12 and decreased both rostrally and caudally. Inhibitory responses to renal nerve stimulation required activation of renal C-fibers. 4. All cells that responded to stimulation of renal afferent fibers received convergent inputs from somatic structures. Forty-four cells were classified as wide dynamic range, 10 were high threshold, 12 were high-threshold cells with inhibitory input from hair, 2 were deep, and 2 were low threshold. Somatic receptive fields were large and located on the flank and abdomen and/or the upper hindlimb. Fourteen cells had inhibitory receptive fields located on the contralateral hindlimb or one of the forearms. 5. It is concluded that T11-L1 STT cells in the monkey respond reliably to renal nerve stimulation. Thoracolumbar STT cells may thus play a role in pain that results from renal disease. The locations of the somatic receptive fields of the cells suggest that they are responsible for the referral of renal pain to the flank and abdomen.

Encoding of electrical, thermal, and mechanical noxious stimuli by subnucleus reticularis dorsalis neurons in the rat medulla.

1. In anesthetized rats, recordings were made within the medullary subnucleus reticularis dorsalis (SRD) from neurons that exhibited convergence of nociceptive inputs from the entire body. Neurons with total nociceptive convergence (TNC) responded to suprathreshold percutaneous electrical stimuli (2-ms duration) with an early and a late peak due to activation of A delta- and C-fibers, respectively, no matter which part of the body was stimulated. Neurons with partial nociceptive convergence (PNC) responded to the same stimuli with an A delta-peak regardless of which part of the body was stimulated and with a C-peak of activation from some, mainly contralateral, parts of the body. The characteristics of the responses of these neurons to the application of graded intensities of electrical, thermal, and mechanical stimuli were analyzed. 2. All TNC neurons and 85% of PNC neurons responded to A delta- and C-fiber activation following percutaneous electrical stimulation of the contralateral hindpaw. With regard to A delta-fiber-evoked responses, a linear relationship between the logarithm of the applied current and the magnitude of the responses was found within the 0.25- to 6.0-mA and 0.5- to 24-mA ranges for TNC and PNC neurons, respectively; however, these curves were essentially similar. With regard to C-fiber-evoked responses, such a linear relationship was found within the 1.5- to 6.0-mA range for both types of SRD neurons, although the TNC neurons presented larger C-fiber-evoked responses than did the PNC neurons. 3. TNC and PNC neurons linearly increased their discharges during the application of noxious thermal stimuli to the contralateral hindpaw within the range 44-52 degrees C; the mean responses evoked by noxious heat from TNC neurons were of higher magnitude than those from PNC neurons. The majority of SRD neurons presented long-lasting afterdischarges, especially with the highest temperature employed (52 degrees C). 4. TNC neurons monotonically increased their discharges during graded mechanical or thermal stimulation of the tail. When mechanical stimuli were applied, a linear relationship was found between the logarithm of the strength of the mechanical stimulus and the neuronal discharges, in the 5.3- to 7.4-N/cm2 range. With thermal stimulation, TNC neurons linearly increased their discharges in the 44-52 degrees C range. When increasing amounts of the tail were immersed in a 50 degrees C waterbath, TNC neurons increased their discharges within a restricted range of tail surface areas (0.9-5.7 cm2); further increases in the stimulated surface size were not followed by increases in firing rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Release of Multiple Tachykinins from Capsaicin-sensitive Sensory Nerves in the Lung by Bradykinin, Histamine, Dimethylphenyl Piperazinium, and Vagal Nerve Stimulation

Recent evidence suggests that activation of airway C-fibers, besides causing afferent transmission, also causes release of transmitters from peripheral endings, probably via local axon reflexes, resulting in effects on vascular and bronchial smooth muscle, i.e., vasodilatation, increase in vascular permeability, and bronchoconstriction. In the present study, the release of tachykinins was investigated in the perfused guinea pig lung by various ways of neuronal activation. Substance-P-like immunoreactivity (SP-LI) and neurokinin-A-like immunoreactivity (NKA-LI) was determined by radioimmunoassay in the perfusates. A significantly increased outflow of both SP-LI and NKA-LI was observed during perfusion of the lung with high potassium concentration (60 mM), the C-fiber activator capsaicin (1 microM), bradykinin (1 microM), histamine (100 microM), or the nicotinic agonist dimethylphenyl piperazinium (DMPP) (32 microM). Release of both SP-LI and NKA-LI could also be achieved by electrical stimulation of vagal nerves. The percental increase varied from 80 to 1,000% depending on the kind of stimulus. The release of tachykinins by K+ or capsaicin was greatly reduced in calcium-free medium. Release by histamine was completely inhibited by 1 microM mepyramine, and release by DMPP was abolished by 20 microM hexamethonium. High performance liquid chromatography indicated that NKA-LI consisted of several cross-reacting substances, presumably other peptides of the tachykinin family. Among the isolated mammalian tachykinins, NKA was the most potent one to contract tracheal smooth muscle of guinea pigs in vitro, followed by neurokinin B and by SP. Both NKA and SP relaxed the guinea pig pulmonary artery with similar potency.(ABSTRACT TRUNCATED AT 250 WORDS)

Centrifugal activity in afferent C-fibers influences the spontaneous afferent barrage generated in nerve-end neuromas

We have investigated the effect of a prolonged, low-frequency impulse barrage on the spontaneous afferent discharge that originates in experimental nerve-end neuromas in the rat sciatic nerve. Centrifugal activity in afferent A-fibers did not affect electrogenesis in the neuroma. When C-fibers were recruited, however, over half of the axons tested were either suppressed or excited. We suggest that these effects resulted from the stimulation-evoked release of neuroactive peptides or related substances from the cut ends of afferent C-fibers.

Barosensory neurons in the rostral ventrolateral medulla mediate the renal-sympathetic reflex in rabbits

In urethane-anesthetized and vagotomized rabbits, activation of C-fibers of renal afferents resulted in a reflex change in multifiber renal nerve activity (RNA) which consisted of inhibitory (I) and excitatory (E) components, either alone or in combination. The I and E components were individually and reversibly blocked by bilateral application of bicuculline and kynurenic acid, respectively, to the ventral surface of medulla. Bicuculline further eliminated the sympathoinhibiton produced by stimulation of the aortic nerve. Within the subjacent rostral ventrolateral medulla (RVLM), we recorded 23 spontaneously active single units that responded to electrical stimulation of renal afferents and were antidromically activated by stimulation of the dorsolateral funiculus at the C2 level. Usually, the neuronal response preceded that of the RNA by about 100 ms. These bulbospinal RVLM neurons were barosensory, since they responded to stimulation of the aortic nerve. We conclude that barosensory neurons in the RVLM mediate the renal-sympathetic reflex in rabbits.

Barosensory neurons in the rostral ventrolateral medulla mediate the renal-sympathetic reflex in rabbits.

In urethane-anesthetized and vagotomized rabbits, activation of C-fibers of renal afferents resulted in a reflex change in multifiber renal nerve activity (RNA) which consisted of inhibitory (I) and excitatory (E) components, either alone or in combination. The I and E components were individually and reversibly blocked by bilateral application of bicuculline and kynurenic acid, respectively, to the ventral surface of medulla. Bicuculline further eliminated the sympathoinhibiton produced by stimulation of the aortic nerve. Within the subjacent rostral ventrolateral medulla (RVLM), we recorded 23 spontaneously active single units that responded to electrical stimulation of renal afferents and were antidromically activated by stimulation of the dorsolateral funiculus at the C2 level. Usually, the neuronal response preceded that of the RNA by about 100 ms. These bulbospinal RVLM neurons were barosensory, since they responded to stimulation of the aortic nerve. We conclude that barosensory neurons in the RVLM mediate the renal-sympathetic reflex in rabbits.

Respiratory changes induced by activation of testicular afferents in dogs

Reportedly, more than 90% of the testicular afferents of the dog are of the polymodal type. The possible involvement of these afferents in modulation of respiration was studied using anesthetized dogs, which had been vagotomized and with both common carotid arteries ligated. Electrical stimulation of the superior spermatic nerve at an intensity of 1/5 Tc (Tc: threshold intensity for C-fiber activation) induced no substantial changes in respiration, while above 1/2 Tc it induced an increase in minute expiratory volume (VE), or a decrease followed by an increase in VE. The pattern of respiratory change was converted from the former to the latter by increasing the stimulation frequency while maintaining the same intensity. Mechanical stimulation of the testis through a stimulator with a tip of 1 cm in diameter caused an increase of VE at 200 g and a decrease followed by an increase of VE above 500 g. Intra-arterial injection of bradykinin (3 x 10(-6) M), hypertonic saline (1.5 M) and high K+ solution (180 mM) to the spermatic artery induced similar respiratory changes. Pneumograms showed a shift in end-expiratory position even at stimulus intensities without significant VE changes. Phrenic nerve recordings from some artificially ventilated dogs, revealed an prolongation of the first expiratory phase followed by augmentation of phrenic activity, mostly an increase in respiratory rate. Comparison between afferent activities and reflex respiratory changes suggests that above described two types of respiratory changes are brought about by the activities of testicular polymodal receptors.

Laser Doppler measurements of skin vasodilation elicited by percutaneous electrical stimulation of nociceptors in humans.

This study was designed to assess the quantitative features of the skin protecting mechanism of axon reflexes by monitoring stimulus related changes in skin blood flow using laser Doppler flowmetry. Skin vasodilatation induced by trains of brief transcutaneous electrical pulses (0.5 ms, 150 V) was strictly related in magnitude to the number of pulses (trains of 1-32). This vascular response was reduced by 95% when the skin had been pretreated by painting it for two days with a 1% alcoholic solution of capsaicin. The sensitivity of vascular responses to activation of afferent C-fibers indicates a role of this mechanism in the protection of the skin against noxious events.

Has the amount of spontaneous electrical activity in experimental neuromas been overestimated?

Previous studies of experimental neuromas have indicated that some axons terminating in the neuroma exhibit both spontaneous and mechanosensitive discharges. Since these spontaneous discharges appear to occur in potentially nociceptive axons (A delta and C fibers), it has been speculated that this activity may relate to pain that occurs after peripheral nerve injury. Recent results from our laboratory have revealed several possible sources of error in prior electrophysiological studies of neuromas. Most notably, gallamine, a muscle-paralyzing agent that has been used in the majority of previous studies of experimental neuromas, has profound potassium-channel-blocking properties that may increase spontaneous activity in damaged axons. The present study was conducted to re-evaluate the incidence of spontaneous activity in experimental neuromas, and the fiber types involved in these discharges. A group of 44 male Sprague-Dawley rats underwent unilateral saphenous axotomy 1-8 weeks prior to acute neurophysiological recording experiments, and 6 additional rats underwent acute control recording procedures only. Recording was performed in all animals using a modification of the microfilament recording technique to determine the conduction velocities (CVs) and origins of spontaneously discharging axons. A thorough search for spontaneous discharges was made in each nerve both before and after the administration of gallamine. Spontaneous activity was rare in acutely severed saphenous nerve and was not significantly affected by gallamine administration. In rats with 1- to 4-week-old experimental saphenous neuromas, spontaneous activity was rare but was increased by a factor of 12.75 after gallamine treatment. Gallamine administration produced significantly more of both A alpha beta and A delta activity, compared to control recordings. No spontaneous C-fiber activity was found originating in neuromas either before or after gallamine. C-fiber spontaneous discharges in the apparently isolated saphenous nerve segment had receptive fields in fascia, superficial vasculature, and hairy skin of the medial hindlimb. Our conclusions are as follows: (1) Neuromas exhibit only rare spontaneous discharges unless exposed to potassium-channel-blocking agents; (2) all C-fiber activity recorded in saphenous nerve with a distal neuroma is derived from vascular, fascial, and other receptive fields rather than from the neuroma; (3) these data are consistent with known clinical phenomena in that neuromas are not usually spontaneously painful.

Involvement of the dorsolateral funiculus in the descending spinal projections responsible for diffuse noxious inhibitory controls in the rat.

Recordings were made from convergent neurons in the lumbar dorsal horn of the spinal cord of the rat. These neurons were activated by both innocuous and noxious mechanical stimuli applied to their excitatory receptive fields located on the extremity of the hindpaw. Transcutaneous application of suprathreshold 2-ms square-wave electrical stimuli to the center of the excitatory field, resulted in responses to C-fiber activation being observed. This type of response was inhibited by applying a noxious thermal conditioning stimulus on the muzzle. The immersion of the muzzle in a 52 degrees C waterbath resulted in a strong reduction of the response during the application of the noxious conditioning stimulus and this was followed by long lasting poststimulus effects. Such inhibitory processes have been termed diffuse noxious inhibitory controls (DNIC). The effects on these inhibitions of lesions including the dorsolateral funiculus (DLF) were investigated in acute experiments: tests were performed before and at least 30 min after the DLF lesion. A lesion including the DLF ipsilateral to the neuron under study completely abolished the inhibitory processes triggered from the muzzle. Concomitantly, a facilitation of C-fiber responses was observed. Nevertheless, DNIC was still impaired even using a juxtathreshold current to elicit a weak C-fiber response. To ascertain further the main, if not entire, participation of the ipsilateral DLF in the descending projections responsible for the heterotopic inhibitory processes, the effects of a lesion of the contralateral DLF were investigated. Neither the inhibitory processes nor the unconditioned C-fiber responses were altered by this procedure. Again, a second lesion including the ipsilateral DLF induced a blockade of DNIC. It is concluded that the descending projections involved in the triggering of DNIC are mainly, if not entirely, confined to the DLF ipsilateral to the neuron under study. The contralateral DLF did not appear to play a role in these processes.

Relative effectiveness of C primary afferent fibers of different origins in evoking a prolonged facilitation of the flexor reflex in the rat

Changes in the excitability of the hamstring flexor withdrawal reflex produced by conditioning stimuli applied to C-afferent fibers of different origins have been examined in the decerebrate spinal rat. In the absence of conditioning stimuli, the flexor reflex elicited by a standard suprathreshold mechanical stimulus to the toes is stable when tested repeatedly for hours. Three categories of conditioning stimuli have been used in an attempt to modify the excitability of the flexor reflex; electrical stimulation of a cutaneous (sural) nerve or a muscle (gastrocnemius-soleus) nerve at C-fiber strength; the application of mustard oil, a chemical irritant that activates chemosensitive C-afferents, to the skin or injected intramuscularly and intraarticularly; and the indirect activation of high-threshold muscle afferents by fused tetanic contractions of the tibial muscles. Conditioning stimuli of an intensity sufficient to activate C-afferent fibers result in a heterosynaptic facilitation of the flexor motoneuronal response to the standard test input, which lasts from 3 min to more than 3 hr, depending on the stimulus and the C-afferents activated. Pretreatment of the sciatic nerve with the C-fiber neurotoxin capsaicin abolishes all the postconditioning facilitations, which is an indication that it is likely that it is C-afferents that are primarily responsible for the facilitatory effects of the conditioning stimuli, although some A delta afferents may contribute. Capsaicin pretreatment does not modify the reflex response to the test stimulus. The most prolonged increase in the excitability of the flexor reflex resulted from intraarticular injections of 5 microliter mustard oil. Using the subsequent injection of lignocaine intraarticulary, it was found that the prolonged facilitation of the reflex is triggered by the afferent input generated by the conditioning stimulus and does not require an ongoing input for its maintenance. These results indicate that there is a spectrum of central changes in the stimulus response relations of the spinal cord resulting from the activation of C-fibers of different origins. The prolonged duration of some of these changes means that the peripheral activation of C-afferents will modify the functional response of the spinal cord to other inputs applied long after the conditioning input, and this may be responsible for some of the sensory and motor alterations found after peripheral tissue injury.

Background activity in pulmonary vagal C-fibers and its effects on breathing

Vagal cooling experiments suggest that the deep show breathing observed after vagotomy results not only from loss of pulmonary stretch receptor feedback, but also from loss of some unidentified vagal input. To investigate this possibility we cooled the vagus nerves in anesthetized dogs. In dogs breathing spontaneously, the Hearing-Breuer reflex was abolished at 7 °C, but average expiratory time was unchanged and lengthened only on cooling below 3 °C,. In artificially ventilated dogs the pulmonary vargus nerves were cooled in the chest and phrenic activity was recorded. Entrainment of phrenic bursts to the ventillator cycle ceased at 7 °C, and expiratory pauses shortened; they lengthened again on cooling below 3 °C. Cervical vagotomy did not change breathing pattern after the pulmonary vagus nerves were cut. Recording of afferent impulses during cooling showed that at 5 °C or less pulmonary vagal input was confined largely to nonmyelinated fibers; at 3 °C, background activity in pulmonary C-fibers was still 78% of control whereas myelinated afferents were virtually silent. We suggest that in eupnea low frequency, background activity in pulmonary afferent C-fibes shortens expiratory time.

Stimulation of pulmonary vagal afferent C-fibers by lung edema in dogs.

In anesthetized, open-chest dogs we examined the effect of pulmonary edema on the firing frequency of afferent vagal fibers arising from the lung. We recorded impulses from slips of the cervical vagus nerves and infused isotonic Krebs-Henseleit solution (20% of body weight) intravenously to increase net filtration pressure in the lung microvasculature. Measurement of extravascular lung water (6.0 +/- 0.4 g/g dry lung), and morphological examination of lung tissue (revealing various degrees of perivascular and peribronchial cuffing) confirmed that edema was present. At the end of the infusion when the lungs were congested (lung microvascular pressure, 37 cm water) and edematous, the impulse frequency of pulmonary and bronchial C-fibers and rapidly adapting receptors had increased 5-6 times. The only significant change in slowly adapting receptor activity was an increase during deflation. When lung water was still elevated but lung microvascular pressure had been restored to control by withdrawal of blood, impulse activity of rapidly and slowly adapting receptors reverted to or below control. Pulmonary C-fiber activity, although less than during congestion, remained significantly above control, several C-fibers being stimulated by interstitial edema in the absence of alveolar edema. Bronchial C-fibers were stimulated in severely edematous lung showing pronounced peribronchial cuffing and alveolar edema, but were not stimulated in milder grades of edema. Our results support the hypothesis (Paintal, 1969) that pulmonary C-fibers (J-receptors) are stimulated by an increase in interstitial pressure secondary to edema.

Ascending pathways in the spinal cord involved in triggering of diffuse noxious inhibitory controls in the rat.

Recordings were made from convergent neurons in trigeminal nucleus caudalis of the rat. These neurons were activated by both innocuous and noxious mechanical stimuli applied to their excitatory receptive fields located on the ipsilateral part of the muzzle. Transcutaneous application of suprathreshold 2-ms square-wave electrical stimuli to the center of the excitatory field resulted in responses to C-fiber activation being observed (mean latencies 63.6 +/- 5.5 ms). This type of response was inhibited by applying noxious conditioning stimuli to heterotopic body areas, namely immersing either the left or right hindpaw in a 52 degrees C water bath. A virtually total block of the response was observed during the application of the noxious conditioning stimulus, and this was followed by long-lasting poststimulus effects. Such inhibitory processes have been termed diffuse noxious inhibitory controls (DNIC) (39, 40). The effects on these inhibitions of various transverse lesions of the cervical spinal cord were investigated in acute experiments; tests were performed before and at least 30 min after the spinal section. While the unconditioned C-fiber responses were unaltered, the inhibitory processes could be impaired by the cervical lesions, although these effects depended on the part of the cervical cord destroyed and the side of application of the conditioning stimulus. Lesioning dorsal, dorsolateral, and ventromedial parts of the cervical cord was found not to affect inhibitory processes triggered from either hindpaw. The overlapping of the regions of these ineffective lesions revealed that two remaining regions were not destroyed, that is, the left and right ventrolateral quadrants. In experiments where the left anterolateral quadrant was affected by the surgical procedure the inhibition triggered from the right hindpaw was strongly reduced, whereas that elicited by left hindpaw stimulation was not diminished. The loss of inhibitory effects was characterized by a complete disappearance of poststimulus effects, whereas inhibition observed during the application of the noxious thermal conditioning stimulus was only partially, albeit very significantly, blocked. To ascertain further the mainly crossed nature of the pathways responsible for the heterotopic inhibitory processes, the effects of lumbar commissurotomy were investigated. Again the unconditioned C-fiber responses were unaltered by this procedure, whereas the inhibitory processes, whether triggered from the left or right hindpaw, were strongly depressed in all the experiments.(ABSTRACT TRUNCATED AT 400 WORDS)

Textbook of Pain

This book, with 79 chapters written by 102 contributors, has three parts: basic science related to pain, clinical conditions with pain, and therapy. The chapters on basic aspects are all uniformly good, and most are excellent. The discussions are well written, succinct, and substantially documented. Written mostly by basic scientists, the book maintains the interest of the clinician reader because the clinical relevance of the discussion is pointed out. Experts on pain may learn a few things. These include the dual action (analgesia and pain-threshold reduction) of substance P, the reasons to doubt that pain is the only result of C-fiber action, and the subdivision of lamina II into an outer (IIo) and an inner (IIi) layer. The subdivision of lamina II is to understand better the analgesia-related circuitry within the dorsal horn; Hi responds only to innocuous light brush while IIo contains specialized nociceptive cells that respond to mechanical

Intrathecal somatostatin modulates spinal sensory and reflex mechanisms: Behavioral and electrophysiological studies in the rat

Using behavioral and electrophysiological techniques, evidence was obtained that somatostatin (SOM) has an excitatory role in spinal sensory and reflex mechanisms of the rat. Intrathecal (i.t.) SOM (1 and 10 μg) induced a dose-dependent caudally directed scratching behavior lasting about 20 min. In decerebrated, spinalized, unanesthetized rats, small doses of i.t. SOM (10 ng−1 μg) increased the excitability of the hamstring flexion reflex. Similar effects on the reflex may be seen after conditioning afferent C-fiber activation. The results indicate that during C-afferent activity SOM may be released and may increase spinal cord excitability.

Long latency spinal cord dorsum potential; suppression by intrathecal morphine and enkephalin analog

We have developed a new method which combines intrathecal recordings of spinal cord dorsum potentials (CDPs) with application of drugs to the spinal cord via an intrathecal catheter. With this technique we have discovered a late component (LC) in the CDP which has not been previously described. The LC is evoked by high intensity electrical stimulation of the rat tail. Whereas previous reports describe early components in the CDP evoked by low intensity A-fiber stimulation, ours is the first to describe a late evoked potential implicating C-fiber activation of the cord. Moreover, we show that the LC is blocked by intrathecal application of morphine sulphate or d-Ala-Met-enkephalinamide in a naloxone reversible manner. We postulate that this LC represents, at least in part, the spinal cord evoked response to C-polymodal nociceptive afferent inputs.