Role Of Afferents Research Articles

ACTIVATION OF RAT PANCREAS MECHANOSENSITIVE SPINAL AFFERENTS IN A NOVEL IN VITRO PREPARATION

Few studies have recorded afferent nerve discharge from the pancreas and the role of afferent nerves in pancreatic physiology and pathophysiology is very poorly understood. Aims: To map and characterise mechanosensitive afferents in the normal rat pancreas. Methods: A preparation consisting of the pancreas, attached spleen and duodenum, and including the pancreatic duct (PD), common bile duct (CBD) and the sympathetic chain was obtained from anaesthetised Sprague Dawley rats (n = 9). The CBD was cannulated. The preparation was placed in a 2 chamber organ bath. Extracellular nerve recordings were obtained from fibers teased from the sympathetic chain adjacent to the coeliac ganglia. Nerve discharge evoked by blunt probing, CBD/PD distension (44 mmHg), or electrical field stimulation (EFS; n = 3; 20 V, 0.5 ms duration) of pancreas was recorded. Results: Discharge from 137 fibers was recorded, of which 50% displayed spontaneous activity. Blunt probing evoked a discharge in 20% of fibers whereas EFS evoked discharge in 11/42 fibers, of which 3 receptive fields responded to blunt probing. Based on conduction velocity measurements (0.36 ± 0.06 m/s; n = 16 fibers), recordings were from C fibers. Mechanosensitive receptive fields were associated with arteries/blood vessels in the pancreas (16/32), pancreas near lymph nodes (2/32), pancreatic tissue (12/32), CBD (1/32) and duodenal mesentery (1/32). Non-mechanosensitive receptive fields were located in pancreatic tissue (5/11), arteries/blood vessels (5/11) or CBD/PD (1/11). CBD/PD distension did not evoke any discharge. Conclusion: Mechanosensitive and non-mechanosensitive afferent nerves are associated with several structures in the pancreas. Their role in physiological and pathophysiological signaling remains to be established. Supported by the FMC Foundation.

Role of afferent nerves and sensory peptides in the mediation of hepatic artery buffer response

Role of afferent nerves and sensory peptides in the mediation of hepatic artery buffer response

Bronchial hyperresponsiveness induced by chronic treatment with albuterol: Role of sensory nerves.

It has recently been suggested that regular treatment with racemic beta(2)-adrenoceptor agonists might result in bronchial hyperresponsiveness (BHR) to a range of spasmogens, and this might be due to adverse effects of the distomer. We sought to determine whether BHR induced by means of continuous exposure to racemic and S-albuterol was mediated by sensory nerves. Naive or ovalbumin-sensitized guinea pigs were treated for 10 days with RS-, R-, or S-albuterol (1 mg.kg(-1).d(-1)) through subcutaneously implanted minipumps. Lung function was then determined in response to a number of spasmogens and assessed on the basis of an increase in total airway resistance. A separate group of animals were chronically treated with capsaicin (80 mg/kg) before the albuterol treatment. Treatment with RS- or S-albuterol increased airway responsiveness to bradykinin, leukotriene C(4), and capsaicin in naive guinea pigs (P <.05) and to histamine and ovalbumin in immunized guinea pigs (P <.05). Chronic treatment with capsaicin prevented the development of RS- and S-albuterol-induced BHR in these models. The bronchodilator efficacy of acute intravenously administered RS-albuterol was unaffected in RS-, R-, or S-albuterol-treated guinea pigs compared with in vehicle-treated animals. We have provided evidence demonstrating that continuous exposure to RS- and S-albuterol increases bronchial responsiveness to a range of stimuli, an effect not attributed to beta-adrenoceptor occupancy or desensitization. Furthermore, capsaicin-sensitive sensory nerves mediate the development of BHR, at least in part.

Pathophysiology of nasal symptoms.

Symptoms are perceived by the patient and all nasal symptoms must eventually relate to stimulation of sensory nerves or some change in the activity of the CNS. Although it is the symptoms that are of prime importance to the patient, the role of sensory nerves and psychology in the generation and perception of symptoms has been relatively neglected compared to the large amount of research on inflammatory mediators. This paper discusses how physical and chemical changes in the nasal epithelium result in the generation of inflammatory mediators that are responsible for symptoms. Inflammatory mediators can cause symptoms in three ways. (1) By having direct action on glands and blood vessels to cause glandular secretion, vasodilation, increased vascular permeability, and transudation of a plasma exudate. (2) By stimulation of sensory nerve endings to cause reflex glandular secretion, sneezing, and sensations such as itching, irritation, pain, and pressure. (3) By effects on the central nervous system to cause, headache, fever, tiredness, and mood changes.

The role of protease-activated receptor-2 (PAR2) in the modulation of beating of the mouse isolated ureter: lack of involvement of mast cells or sensory nerves.

1 The localization of protease-activated receptor-2 (PAR2) and the effects of PAR2 activators were investigated in the mouse isolated ureter in order to test the hypothesis that PAR2 activation may initiate neuropeptide release from sensory nerve fibres and hence contribute to inflammation. 2 PAR2 was localized by fluorescence immunohistochemistry to both the smooth muscle and epithelium of the ureter. Macrophage-like cells in the adventitia of the ureter were also PAR2-immunoreactive. PAR2-immunoreactivity was not observed in mast cells or nerve fibres. 3 In circular muscle preparations of the ureter in which continuous rhythmic beating was induced by KCl (20 mM) and the thromboxane A2 mimetic U46619 (0.3 microM), trypsin (0.3 U ml-1) reduced beat frequency to 84.6+/-2.0% of control rates. The PAR2-selective peptide agonist SLIGRL-NH2 concentration-dependently (0.1-3.0 microM) slowed beat frequency to a maximum of 72.7+/-2.0%. 4 Histamine (1-300 microM) was more efficacious than SLIGRL-NH2 in inhibiting ureter beat frequency in a concentration-dependent manner to a maximum (at 300 microM) of 7.9+/-2.5% of the control rate. 5 Pretreatment of preparations with capsaicin (10 microM for 30 min) markedly attenuated the inhibitory effect of histamine, but not that of SLIGRL-NH2, indicating a role for sensory nerves in the inhibitory effect of histamine only. 6 The inhibitory effect of SLIGRL-NH2 on ureter beat frequency was unaffected by the nitric oxide (NO) synthase inhibitor, L-NOARG (100 microM) or the cyclo-oxygenase inhibitor, indomethacin (3 microM). 7 In conclusion, PAR2 activation causes inhibition of beating in the mouse ureter that is not mediated by axon reflex release of inhibitory neuropeptides. This inhibitory effect of PAR2 appears to be mediated directly on smooth muscle cells, although the contribution of non-NO, non-prostanoid epithelium-derived factors cannot be ruled out.

A Role for Neuropeptides in UVB-Induced Systemic Immunosuppression

The aim of this study was to investigate the possible role of sensory nerves in UV light-induced systemic immunomodulation. Contact hypersensitivity to the low molecular weight compound picrylchloride was used as a model for cellular immunity that can be suppressed by low (i.e. suberythemal) doses of UV light even after exposure at a distant locus (i.e. systemic immunosuppression). In sensory nerve-depleted mice, achieved by two subcutaneous injections with the neurotoxin capsaicin before the age of 4 weeks, UV light exposure failed to inhibit contact hypersensitivity responses to picrylchloride. This indicates that sensory nerves are at least partially involved in the induction of systemic immunosuppression by UV light. In order to analyze whether sensory neuropeptides, such as calcitonin gene-related peptide (CGRP) and tachykinins, are involved in UV light-induced systemic immunosuppression, mice were pretreated with selective antagonists prior to each UV light exposure. These experiments indicated that CGRP but not the tachykinins plays a crucial role in the UV light-induced systemic immunosuppression.

A Role for Neuropeptides in UVB-Induced Systemic Immunosuppression

The aim of this study was to investigate the possible role of sensory nerves in UV light-induced systemic immunomodulation. Contact hypersensitivity to the low molecular weight compound picrylchloride was used as a model for cellular immunity that can be suppressed by low (i.e. suberythemal) doses of UV light even after exposure at a distant locus (i.e. systemic immunosuppression). In sensory nerve-depleted mice, achieved by two subcutaneous injections with the neurotoxin capsaicin before the age of 4 weeks, UV light exposure failed to inhibit contact hypersensitivity responses to picrylchloride. This indicates that sensory nerves are at least partially involved in the induction of systemic immunosuppression by UV light. In order to analyze whether sensory neuropeptides, such as calcitonin gene-related peptide (CGRP) and tachykinins, are involved in UV light-induced systemic immunosuppression, mice were pretreated with selective antagonists prior to each UV light exposure. These experiments indicated that CGRP but not the tachykinins plays a crucial role in the UV light-induced systemic immunosuppression.

Mediation of prostaglandin f2a-induced ocular surface hyperemia by sensory nerves in rabbits

PURPOSE. Prostaglandin F 2a (PGF 2a) and several other prostaglandins cause surface hyperemia of the eye when applied topically. The purpose of the present study was to investigate the role of sensory nerves in prostaglandin-induced ocular hyperemia. METHODS. The ophthalmic branch of the trigeminal nerve was unilaterally electrocoagulated in rabbits using a stereotaxic technique. Two weeks later the animals received bilaterally one drop of PGF 2a -isopropyl ester (PGF 2a -IE) at a dose of 1 µg/ eye. The blood flow to the different parts of the eye was measured with the radioactively labeled microsphere technique before, 30 and 60 min after treatment with PGF 2a -IE. RESULTS. In the control eyes with intact sensory innervation, PGF 2a -IE caused a marked increase in blood flow to the surface structures of the eye (conjunctiva, anterior sclera, eyelids and nictitating membrane) and the iris, and a moderate increase in the blood flow to the ciliary processes, but no increase in the choroidal blood flow. In the denervated eyes the increase in blood flow to the surface structures was almost completely abolished, and there was also a tendency toward less increase in blood flow in the anterior uvea. CONCLUSIONS. These results indicate that PGF 2a -induced ocular surface hyperemia, at least at the early stage, is mediated to a large extent by sensory nerves.

A mechanism for sympathectomy-induced bone resorption in the middle ear.

Recent investigations have demonstrated a link between sympathectomy and osteoclast-mediated bone resorption. The exact nature of this link, however, is unknown. We hypothesize that substance P, a potent vasoconstrictive neuropeptide found in peripheral sensory fibers, including those innervating bone, is the mediator of this phenomenon. To test this theory, the effects of substance P on in vitro calcium release from cultured neonatal mouse calvaria were assessed. In addition, an in vivo study was conducted whereby gerbils were injected with capsaicin to eliminate substance P-containing fibers before sympathectomy with 6-hydroxydopamine. If the effects of 6-hydroxydopamine were eliminated by prior administration of capsaicin, the role of sensory nerves in sympathectomy-induced resorption would be strongly implicated. Substance P at 10(-8) mol/L was incubated with eight newborn Swiss-Webster mouse hemicalvarial explants and compared with explants incubated in control media alone. The neonatal mice were euthanized at day 3, and their hemicalvaria were preincubated in 2 ml of stock media without treatment for 24 hours at 36.5 degrees C as a stabilization period. After the stabilization period, the stock media were replaced with 2 ml of fresh control media or media containing substance P at 10(-8) mol/L. A similar experiment was performed with the addition of indomethacin at 5 x 10(-7). The explants were then incubated for 72 hours with gassing every 12 hours with a mixture of O2, N2, and CO2. At the end of the 72-hour period, the media were analyzed for calcium content by atomic absorption spectrophotometry and compared by one-way analysis of variance with Bonferroni-corrected post hoc tests. Forty-eight Mongolian gerbils were placed into four groups: group 1 received intraperitoneal injections of 6-hydroxydopamine at 75 micrograms/gm body weight on days 1, 2, 6, 7, and 8; group 2 received identical injections of hydroxydopamine, but 12 hours after receiving subdermal injections of capsaicin at 50 micrograms/gm body weight; group 3 received only subdermal injections of capsaicin; and group 4 received only saline injections to serve as controls. Seven days after treatment, the animals were euthanized, and the ventral wall of each animal's right bulla was resected and quantified for osteoclast number and surface with a computer-based histomorphometry system. Analysis was then made by one-way analysis of variance with Bonferroni-corrected post hoc tests. The results of the in vitro study revealed that substance P at 10(-8) mol/L (11.05 +/- 3.37 micrograms/ml) induced significant calcium release from cultured neonatal mouse calvaria when compared with control bone incubated in base media alone (0.92 +/- 2.85 micrograms/ml, p < 0.01). The process was completely inhibited by 5.0 x 10(-7) indomethacin. The results of the in vivo study showed 6-hydroxydopamine treatment significantly increased both the osteoclast number (NOc/TL = 3.14 +/- 1.33/mm) and the osteoclast surface (OcS/BS = 16.04% +/- 6.95%) of bone when compared with bone from saline-treated controls (NOc/TL = 1.77 +/- 0.79/mm, p < 0.01; OcS/BS = 8.88% +/- 4.15%, p < 0.01). These 6-hydroxydopamine-induced increases were eliminated, however, in animals pretreated with capsaicin before sympathectomy (NOc/TL = 1.86 +/- 0.68/mm, p > 0.05; OcS/BS = 9.92 +/- 3.73, p > 0.05), whereas treatment with capsaicin alone had no effect when compared with bone from saline-treated controls (NOc/TL = 2.02 +/- 0.50/mm, p > 0.05; OcS/BS = 10.28% +/- 2.62%, p > 0.05). Substance P has thus been shown to induce calcium release from membranous bone in vitro, whereas capsaicin, a substance P-specific sensory neurolytic chemical, eliminates the in vivo osteoclast-inductive effects of 6-hydroxydopamine when given 12 hours before treatment. The results indicate that substance P is capable of inducing resorption and that substance P-containing sensory ne

A mechanism for sympathectomy-induced bone resorption in the middle ear

BACKGROUND: Recent investigations have demonstrated a link between sympathectomy and osteoclast-mediated bone resorption. The exact nature of this link, however, is unknown. We hypothesize that substance P, a potent vasoconstrictive neuropeptide found in peripheral sensory fibers, including those innervating bone, is the mediator of this phenomenon. To test this theory, the effects of substance P on in vitro calcium release from cultured neonatal mouse calvaria were assessed. In addition, an in vivo study was conducted whereby gerbils were injected with capsaicin to eliminate substance P–containing fibers before sympathectomy with 6-hydroxydopamine. If the effects of 6-hydroxydopamine were eliminated by prior administration of capsaicin, the role of sensory nerves in sympathectomy-induced resorption would be strongly implicated. IN VITRO STUDY: Substance P at 10 -8 mol/L was incubated with eight newborn Swiss-Webster mouse hemicalvarial explants and compared with explants incubated in control media alone. The neonatal mice were euthanized at day 3, and their hemicalvaria were preincubated in 2 ml of stock media without treatment for 24 hours at 36.5° C as a stabilization period. After the stabilization period, the stock media were replaced with 2 ml of fresh control media or media containing substance P at 10 -8 mol/L. A similar experiment was performed with the addition of indomethacin at 5 × 10 -7. The explants were then incubated for 72 hours with gassing every 12 hours with a mixture of O 2, N 2, and CO 2. At the end of the 72-hour period, the media were analyzed for calcium content by atomic absorption spectrophotometry and compared by one-way analysis of variance with Bonferroni-corrected post hoc tests. IN VIVO STUDY: Forty-eight Mongolian gerbils were placed into four groups: group 1 received intraperitoneal injections of 6-hydroxydopamine at 75 μg/gm body weight on days 1, 2, 6, 7, and 8; group 2 received identical injections of hydroxydopamine, but 12 hours after receiving subdermal injections of capsaicin at 50 μg/gm body weight; group 3 received only subdermal injections of capsaicin; and group 4 received only saline injections to serve as controls. Seven days after treatment, the animals were euthanized, and the ventral wall of each animal's right bulla was resected and quantified for osteoclast number and surface with a computer-based histomorphometry system. Analysis was then made by one-way analysis of variance with Bonferroni-corrected post hoc tests. RESULTS: The results of the in vitro study revealed that substance P at 10 -8 mol/L (11.05±3.37 μg/ml) induced significant calcium release from cultured neonatal mouse calvaria when compared with control bone incubated in base media alone (0.92±2.85 μg/ml, p < 0.01). The process was completely inhibited by 5.0 × 10 -7 indomethacin. The results of the in vivo study showed 6-hydroxydopamine treatment significantly increased both the osteoclast number (NOc/TL = 3.14±1.33/mm) and the osteoclast surface (OcS/BS = 16.04%±6.95%) of bone when compared with bone from saline-treated controls (NOc/TL = 1.77±0.79/mm, p < 0.01; OcS/BS = 8.88%±4.15%, p < 0.01). These 6-hydroxydopamine–induced increases were eliminated, however, in animals pretreated with capsaicin before sympathectomy (NOc/TL = 1.86±0.68/mm, p > 0.05; OcS/BS = 9.92±3.73, p > 0.05), whereas treatment with capsaicin alone had no effect when compared with bone from saline-treated controls (NOc/TL = 2.02±0.50/mm, p > 0.05; OcS/BS = 10.28%±2.62%, p > 0.05). Substance P has thus been shown to induce calcium release from membranous bone in vitro, whereas capsaicin, a substance P–specific sensory neurolytic chemical, eliminates the in vivo osteoclast-inductive effects of 6-hydroxydopamine when given 12 hours before treatment. The results indicate that substance P is capable of inducing resorption and that substance P–containing sensory nerves are required for the induction of resorption after sympathectomy in the gerbil. (OTOLARYNGOL HEAD NECK SURG 1995;113:569-81.)

Sensory nerve- and neuropeptide-mediated relaxation responses in airways of Sprague-Dawley rats

We examined the role of sensory nerves in mediating nonadrenergic inhibitory responses in airway segments isolated from male Sprague-Dawley rats. In the presence of adrenergic blockade, capsaicin (Cap; 1 microM) elicited marked relaxation responses in isolated bronchi precontracted with bethanechol (Beth). Cap-induced inhibitory responses were unaffected by tetrodotoxin (TTX), were attenuated by incubation of the airway with indomethacin (Indo), phosphoramidon, or RP-67580, but were abolished by previous exposure of the airway to Cap and by denuding the epithelium. Substance P (SP; 1 microM), neurokinins A and B (1 microM), and calcitonin gene-related peptide (0.1 microM) relaxed Beth-contracted airway segments to a similar extent. The SP-induced responses were unaffected by adrenergic blockade or by pretreatment with either TTX, phosphoramidon, or Cap, but were attenuated by RP-67580 and abolished by Indo and by denuding the epithelium. In anesthetized mechanically ventilated rats, Cap (50 and 100 micrograms/kg i.v.) elicited a dose-dependent reversal of the increase in lung resistance induced by an infusion of Beth. The Cap-induced bronchodilation was unaffected by pretreatment with propranolol alone or in combination with hexamethonium. SP (44 nmol/kg iv) also evoked bronchodilatory responses in intact animals, which were unaffected by propranolol and hexamethonium but were abolished by treatment of the animals with Indo. Electrical-field stimulation (EFS) evoked nonadrenergic noncholinergic relaxation responses in contracted airway segments. These EFS-induced inhibitory responses were markedly attenuated by treatment of the airway segment with TTX, Cap, or RP-67580. We conclude that neuropeptides released from Cap-sensitive sensory nerves have potent inhibitory effects in rat airways that are mediated, in part, by activation of neurokonin NK1 receptors on epithelium and subsequent release of an inhibitory prostaglandin(s).

Gastric adaptation to stress: role of sensory nerves, salivary glands, and adrenal glands.

Single exposure to water immersion and restraint stress (WRS) in rats produces acute gastric mucosal damage, but repetitive WRS insults lead to gastric adaptation to stress ulcerogenesis. This study was designed to assess the mechanism of this adaptation, particularly the role of sensory nerves, salivary glands, adrenal glands, and gastric acid secretion. WRS was applied for a standard period of 3.5 h, either once or repeated every other day for up to 8 days in intact rats and in animals with capsaicin-induced deactivation of sensory nerves, vagotomy, salivectomy, adrenalectomy, and inhibition of gastric acid secretion by H2-blocker. WRS applied once produced multiple gastric erosions accompanied by a significant increase in gastric acid secretion and a decrease in gastric blood flow (GBF) and DNA synthesis. Repeated WRS insults resulted in a significant decrease in the number of gastric lesions, reaching a maximum after four consecutive exposures to WRS. This adaptation to stress ulcerogenesis was accompanied by a decrease in gastric acid secretion and an increase in GBF and mucosal generation of DNA synthesis. Salivectomy, which decreased the luminal content of epidermal growth factor (EGF) (by about 80%), markedly attenuated this adaptation, and this was reversed by the addition of exogenous EGF. Capsaicin-induced ablation of sensory nerves eliminated gastric adaptation to WRS, and this was accompanied by a significant decrease in the GBF, but pretreatment with calcitonin gene-related peptide restored gastric adaptation to stress in capsaicin-denervated rats. Selective vagotomy and adrenalectomy failed to affect gastric adaptation to WRS, whereas gastric acid inhibition by ranitidine enhanced this adaptation. The stomach is able to adapt to repeated stress insults by enhancing GBF and DNA synthesis, and this adaptation is mediated, at least in part, by sensory nerves and EGF.

Regulatory roles of sensory nerves in the gut

Regulatory roles of sensory nerves in the gut

Role of neurogenic inflammation in antigen-induced vascular extravasation in guinea pig trachea.

Conflicting results have been reported about the role of sensory nerves in the allergen-induced plasma extravasation in sensitized guinea pigs using capsaicin desensitization. To investigate the role of tachykinins released from sensory nerves in the anaphylactic reaction in guinea pigs in vivo, we used a selective inhibitor of neutral endopeptidase, phosphoramidon, and a selective neurokinin (NK)-1 receptor antagonist, CP-96,345. Male Hartley guinea pigs were sensitized to OVA by two i.p. injections (70 mg) at 1-wk intervals. Two wk later, the animals were anesthetized and OVA was administered for 2 min by aerosol through a tracheal cannula. Plasma extravasation was assessed by the photometric measurement of the extravasated Evans blue after formamide extraction. Administration of aerosolized OVA to sensitized guinea pigs increased dye extravasation in the trachea in a dose-dependent manner, an effect that was demonstrable 5 min after exposure to allergen and that reached a maximum 10 min after exposure. At 5 min after OVA (5%), phosphoramidon (2.5 mg/kg, i.v.) did not increase the amount of dye in the trachea significantly and CP-96,345 (4 mg/kg) did not decrease the extravasated dye. At 10 min after OVA, allergen-induced plasma extravasation was potentiated by phosphoramidon by 56%, and was inhibited by CP-96,345 (4 mg/kg) by 42%. In the presence of phosphoramidon, CP-96,345 reduced the OVA-evoked plasma extravasation at 10 min in a dose-related manner (0.1-4 mg/kg). CP-96,345 (4 mg/kg) did not affect plasma extravasation induced by platelet-activating factor (100 nmol/kg, i.v.). These results suggest that tachykinin release from sensory nerves after allergen challenge to airways in sensitized guinea pigs is not responsible for the early increase in plasma extravasation, but, tachykinin release appears to play an important role in the subsequent extravasation.

The Role of Sensory Nerves in Catheter-Induced Urethral Inflammation

We have studied the contribution of the nervous system on experimentally induced urethral inflammation in the rat. Urethral inflammation was produced by inserting latex strips into the urethra. The effects of different experimental procedures were assessed by using a 4-grade inflammation scale based on histological findings. Attenuation of urethral inflammation was produced by administration of capsaicin at birth. A more complete attenuation was produced by infusion of capsaicin prior to application of the latex strip. These data taken together indicate that sensory innervation of the urethral mucosa is involved in the inflammatory reaction and that infusion of the urethra with capsaicin may be tried to prevent catheter-induced urethral inflammation.

Neonatal capsaicin treatment prevents insulin-stress-induced adrenal catecholamine secretion in vivo: Possible involvement of sensory nerves containing substance P

We have investigated the effects of neonatal capsaicin treatment on stress-induced catecholamine release from adult rats in vivo. Catecholamines released into the inferior vena cava following insulin injection were separated by HPLC and measured by electrochemical detection. Neonatal capsaicin treatment depleted the substance P levels in the splanchnic nerve of adult rats by 70% and prevented the insulin-induced hypoglycaemia from evoking release of adrenaline. The results of this study provide the first evidence in vivo for the neuromodulatory role of sensory nerves containing substance P in the secretion of catecholamines from the adrenal medulla.

Role of sensory nerves in the cardiovascular and respiratory changes with isometric forearm exercise in man.

1. To investigate the stimulus to the cardiovascular and respiratory systems during isometric exercise, two patients with sensory neuropathies affecting forearm afferent nerves were studied and their circulatory and respiratory responses compared with those of normal subjects. The contribution of pain to the cardiorespiratory changes was also investigated in normal subjects by using hypnosis to relieve pain during and after isometric exercise. 2. The patients and normal subjects performed fatiguing isometric forearm exercises on a handgrip dynamometer on at least two occasions, once with normal forearm circulation and once with the forearm circulation occluded by an arterial cuff during and after exercise. Blood pressure, heart rate, minute ventilation, oxygen consumption and ventilatory equivalent were measured before, during and after exercise. 3. During exercises with and without occlusion increases in blood pressure and heart rate in patients and in subjects under hypnosis were similar to those in control subjects. Changes in oxygen consumption were also similar to those of controls, but the patients showed a smaller rise in ventilation and no increase in ventilatory equivalent. 4. After exercise in normal subjects occlusion of the forearm circulation produced continued elevation of blood pressure and respiration. Blood pressure also remained elevated after exercise with occlusion in subjects under hypnosis, but not in patients with sensory loss. Respiration did not remain elevated in either subjects under hypnosis or patients. 5. The results suggest that cardiovascular and respiratory changes during isometric exercise can occur without involvement of muscle sensory nerves and that pain contributes substantially to the increase in respiration. Normal sensory innervation is apparently necessary only for maintenance of raised blood pressure after exercise with occlusion.

Role of Afferent Nerves in Response of Vasomotor Center to Oxygen Deficiency.

Through numerous investigations it is known that the increased respiratory response to CO2 is due less to its effect on peripheral receptors than on the respiratory center itself, whereas a similar response to oxygen deficiency occurs only when the carotid sinus nerves are intact. The removal of the afferent fibers by elimination of all known ”buffer nerves” results in a failure of respiration during O2 deficiency (Selladurai and Wright,1 Schmidt,2 v. Euler and Liljestrand,3 Smyth,4 Gemmill and Reeves,5 and Wright,6 but cf. Dautrebande and Wegria7). Under such circumstances the blood pressure reaction to O2 deficiency may also be converted from the rise obtained in the intact animal to a fall (Selladurai and Wright,1 and Brewer8. However, the question whether the organization of the vasomotor center is similar to that of the respiratory center can only be investigated when the respiration is kept constant and thereby secondary effects of a reduced respiratory volume eliminated.Such studies were carried ou...