Removal Of Ganglion Research Articles

Cyclophosphamide cystitis in rats: involvement of capsaicin-sensitive primary afferents

The involvement of capsaicin-sensitive primary afferent neurons in cyclophosphamide (CYP)-induced cystitis has been investigated in rats. CYP (150 mg/kg) was administered 48 h before testing in both vehicle- and capsaicin- (50 mg/kg s.c., 4 days before) treated rats. Some experiments were also performed 96 h after bilateral removal of pelvic ganglia to produce bladder denervation. CYP administration produced a marked detrusor hyperreflexia which was abolished by capsaicin pretreatment, demonstrating that it is mediated through stimulation of capsaicin-sensitive afferent neurons. CYP administration was followed by a marked increase in bladder weight and plasma protein extravasation (measured by the Evans blue leakage technique). The latter effect was largely prevented by ganglionectomy but was aggravated by capsaicin pretreatment. The effect of capsaicin was suppressed by ganglionectomy. Isolated strips of detrusor muscle from CYP-treated animals developed less tension in response to various stimuli as compared to strips from vehicle-treated animals; however, when contractile responses were expressed as percentage of an internal standard (carbachol-induced contraction) no difference was evident between the two groups. The bladder content of calcitonin gene-related peptide, used as a marker of the bladder afferent fibres that are capsaicin-sensitive in adult rats, was slightly reduced as compared to controls, but the difference can be accounted for by the increased bladder weight. We conclude that CYP-induced cystitis is not accompanied by a toxic effect on bladder nerves and that the decrease in bladder capacity is entirely mediated through stimulation of capsaicin-sensitive afferent fibres, presumably linked to the formation of the irritant metabolite of CYP, acrolein. At the time chosen as the end point in these experiments after CYP administration, capsaicin-sensitive afferents seem to play an antiinflammatory influence on CYP-induced cystitis.

Direct contact between sympathetic neurons and rat cardiac myocytes in vitro increases expression of functional calcium channels.

To test the hypothesis that direct contact between sympathetic neurons and myocytes regulates expression and function of cardiac Ca channels, we prepared cultures of neonatal rat ventricular myocytes with and without sympathetic ganglia. Contractile properties of myocytes were assessed by an optical-video system. Contractility-pCa curves showed a 60% greater increase in contractility for innervated myocytes compared with control cells at 6.3 mM [Ca]0 (n = 8, P less than 0.05). Cells grown in medium conditioned by growth of ganglia and myocytes were indistinguishable physiologically from control cells. [Bay K 8644]-contractility curves revealed a 60 +/- 10% enhancement of the contractility response at 10(-6) M for innervated cells compared with control cells. The increased response to Bay K 8644 was not blocked by alpha- or beta-adrenergic antagonists. Moreover, increased efficacy of Bay K 8644 was maintained for at least 24 h after denervation produced by removal of ganglia from the culture. Dihydropyridine binding sites were assessed with the L channel-specific radioligand 3[H]PN200-110. PN200-110 binding sites were increased by innervation (51 +/- 5 to 108 +/- 20 fmol/mg protein, P less than 0.01), with no change in KD. Peak current-voltage curves were determined by whole-cell voltage clamp techniques for myocytes contacted by a neuron, control myocytes, and myocytes grown in conditioned medium. Current density of L-type Ca channels was significantly higher in innervated myocytes (10.5 +/- 0.4 pA/pF, n = 5) than in control myocytes (5.9 +/- 0.3 pA/pF, n = 8, P less than 0.01) or myocytes grown in conditioned medium (6.2 +/- 0.2 pA/pF, n = 10, P less than 0.01). Thus, physical contact between a sympathetic neuron and previously uninnervated neonatal rat ventricular myocytes increases expression of functional L-type calcium channels as judged by contractile responses to Ca0 and Bay K 8644, as well as by electrophysiological and radioligand binding properties.

Bradykinin modulation of a spinal nociceptive reflex in the rat

Bradykinin (BK) is a potent algesic compound. Therefore, we hypothesized that BK, acting as a peripheral noxious stimulus, would attenuate or inhibit responses to another noxious stimulus. When administered intravenously (i.v.) to rats lightly anesthetized with pentobarbital, BK, produced a dose-dependent (12–144 μg/kg) inhibition of the nociceptive tail-flick (TF) reflex. BK also produced a dose-dependent decrease in mean arterial blood pressure, a subsequent increase in heart rate and an increase in the rate of respiration. The latency to the maximal effect of BK on the TF reflex was 10 s and was occasionally preceded by pseudoaffective responses at doses greater than 48 μg/kg BK. Neonatal treatment with capsaicin (50 mg/kg, subcutaneous) significantly attenuated BK-produced inhibition of the TF reflex indicating that BK was acting via peripheral afferents to inhibit the TF reflex. Reversible cold block or complete spinal transection at a low thoracic level (T 9–12), but not reversible cold block at a high cervical level (C 1–2), significantly attenuated BK-produced inhibition of the TF reflex, suggesting that BK activates afferents which enter the spinal cord between C 2 and T 9. Pretreatment with intrathecally administered phentolamine (30 μg), an α-adrenoceptor antagonist, or methysergide (30 μg), a non-selective serotonin receptor antagonist, did not alter BK-produced inhibition of the TF reflex, further supporting the absence of activation of descending systems from the brainstem by i.v. BK. While coadministration of PGE 2 and BK significantly potentiated BK-produced inhibition of the TF reflex, neither bilateral removal of the stellate ganglion nor bilateral cervical vagotomy significantly affected the inhibitory action of i.v. BK on the TF reflex. These results suggest that i.v. BK inhibits the nociceptive TF reflex by activation of capsaicin-sensitive visceral afferents entering the spinal cord between C 2 and T 9.

Surgical removal of the sphenopalatine ganglion. Report of three operations; elaborating an original technic to expose the pterygopalatine fossa, command the internal maxillary artery and its terminals and the infraorbital nerve and its branches. 1937.

Surgical removal of the sphenopalatine ganglion. Report of three operations; elaborating an original technic to expose the pterygopalatine fossa, command the internal maxillary artery and its terminals and the infraorbital nerve and its branches. 1937.

Short-day stimulation of testicular activity and immunoreactivity of the hypothalamic GnRH system in mink following deafferentation of the pineal body by bilateral superior cervical ganglionectomy and melatonin replacement

The effects of superior cervical ganglionectomy on testicular function (testis volume and plasma testosterone levels) and the immunocytochemical activity of the GnRH hypothalamic system were studied in the mink, a short-day breeder. Animals reared in a natural photo-period were (i) ganglionectomized at four different times during the period extending from the end of summer to the end of autumn (September 15, October 20, October 28, and December 1), and (ii) reared for 50 days in a short gonadostimulatory photoperiod (4L:20D). Lastly, an attempt was made to overcome the effects of superior cervical ganglion removal by administering melatonin to mink reared in a natural photoperiod. In mink reared in a natural photoperiod, deafferentation of the pineal on September 15 ( L= 12.5h) or October 20 ( L= 10.5h) resulted in consistently low values of testicular volume and plasma testosterone until the end of the experiment (February). When the operation was performed on October 28 ( L= 10h) testicular activity was initiated but only lasted a short time and did not allow maximal gonadal development. When superior cervical ganglionectomy was carried out on December 1 ( L= 8.5h), during the phase of renewed testicular activity, the increases in testicular volume and testosterone levels were not affected by the operation and the subsequent variation of these parameters was identical to that observed in intact animals. Similarly, in mink reared for 50 days in a photoperiod of 4L:20D before superior cervical ganglionectomy, deafferentation of the pineal did not prevent gonadostimulation induced by short days. These results show that once the hypothalamic system secreting GnRH is triggered by short days, its activity is no longer controlled by the photoperiod. The immunohistochemical study of GnRH-secreting hypothalamic neurons, carried out in December without prior colchicine treatment in animals ganglionectomized in September or October, showed the presence of only a small number of GnRH-positive perikarya. Similarly, positive axonal endings in the external layer of the median eminence were scarce and weakly immunoreactive. On the other hand, in intact animals, in those ganglionectomized on December 1, and those exposed to the short photoperiod of 4L:20D, perikarya and immunoreactive endings were numerous and intensely labeled. In mink ganglionectomized in October ( L= 10.5h) and thereby maintained in a phase of sexual quiescence, insertion of melatonin implants in January triggered testicular activity 50 days later.

Nerve growth factor and septal grafts: a study of behavioral recovery following partial damage to the septum in rats

Previous studies have produced conflicting results about the effects of intracerebral injection of NGF after septal damage in rats: in one experiment, behavioral deficits in maze tasks were exacerbated by NGF administration whereas they were alleviated in another one. The present investigation aimed to clarify the effects of NGF and to identify factors liable to induce different behavioral outcomes. Behavioral effects were assessed following a postsurgical delay of five months using various parameters: food consumption in a novel environment, spontaneous activity, locomotion in an open-field, immobility in a tail suspension test, spontaneous alternation in a T-maze and performance in a radial eight-arm maze. Possible influence of intrahippocampal sympathetic fiber ingrowth occurring after septal lesions was ruled out, as the comparison of rats subjected to superior cervical ganglia removal with their lesion-control counterparts showed few behavioral differences, even after NGF administration. All lesioned rats showed reduced adaptability in most of these tests. Grafts partially reversed the lesion-induced deficit in spontaneous alternation. A single intracerebral NGF injection was found to ameliorate radial maze performance, whether rats were grafted or not. However, it appeared that the number of strategies available to NGF-rats in the radial maze task was as limited as for lesion-control rats. These findings suggest that NGF-rats do not recover spatial abilities lost after septal lesions, but are able to make more efficient use of remaining capacities to master the maze task.

Characterization of coronary vasoconstriction produced by rostral ventrolateral medulla stimulation in rats.

Previous studies have demonstrated that coronary vasoconstriction can be produced by activation of specific central nervous system sites in the cat. The present study was undertaken 1) to develop a rat model for studying central influences on coronary circulation and 2) to utilize this model for characterization of the changes in coronary blood flow (CBF) produced by stimulation of rostral ventrolateral medulla (RVLM). Electrical stimulation of right RVLM in chloralose-anesthetized rats with bilateral vagotomy produced a transient decrease in CBF followed by an increase in CBF concomitant with a decrease in hindquarter blood flow, a pressor response, and tachycardia. After atenolol the tachycardia and increase in CBF were abolished, whereas the decrease in CBF was enhanced and prolonged. Phentolamine (1 mg/kg iv) or removal of the stellate ganglia inhibited the decrease in CBF but did not totally abolish the increase in coronary vascular resistance. Inhibition of nitric oxide synthesis with N-nitro-L-arginine (10 microM/kg iv) enhanced the decrease in CBF produced by stimulation in RVLM. These results indicate that, in rat model, the centrally induced decrease in CBF is 1) mediated by cardiac sympathetic innervation but only partially through alpha-adrenoceptors and 2) enhanced by removal of the inhibitory effect of the endothelium.

Extended thoracoscopic T2-sympathectomy in treatment of hyperhidrosis: experience with 130 consecutive cases.

A new method of thoracoscopic T2-sympathectomy mentioned in a previous report was used on 36 cases of hyperhidrosis at Tainan Municipal Hospital in Taiwan between October 1, 1989 and July 31, 1990. To reduce the possibility of incomplete resection of sympathetic nerve tracts, including ganglions and their regeneration, the method was modified on August 1, 1990. Thereafter, routine total removal of T2 and T3 sympathetic ganglions, as well as wide lateral incisions of the pleura on the second, third, and fourth rib beds were performed for treatment of hyperhidrosis. This newly modified method, "extended thoracoscopic T2-sympathectomy," can be performed easily by thoracoscopic approach in the treatment of hyperhidrosis palmaris. From August 1, 1990 to May 31, 1991, 130 consecutive cases of hyperhidrosis (56 males and 74 females) ranging in age from 8 to 51 years underwent extended thoracoscopic T2-sympathectomy. In addition to a nearly 100% cure rate of hyperhidrosis palmaris, significant saving in operative time and hospital stay were achieved. High simultaneous cure rate (70.6%) and subjective improvement (17.4%) of excessive sweating of feet (hyperhidrosis plantaris) were also noted in the 109 cases followed up, and complications were minor. Extended thoracoscopic T2-sympathectomy is not only a time-saving method but also a very simple and effective method in the treatment of hyperhidrosis. It is worthy of being propagated worldwide.

Immunohistochemistry of the Scarpa's ganglion and the crista ampullaris of patients with Menière disease

In certain long-lasting cases of Menière's disease with recurrent attacks, despite of saccotomy, the removal of the vestibular ganglion is the only procedure that relieves vertigo. During ganglionectomy of this group of patients all fresh tissues gotten and gathered from operation are frozen immediately and preserved for immunohistochemical assay with direct and indirect incubations. The positive findings such as ASMA+, AEA+ and ANA+ in tissues of patient's own as well as in control tissues further confirmed the results previously reported by us. The immune-complex mediated arteriolar and capillary vasculitis on the basis of an autoimmune disorder as a secondary autoimmune marker might play a dominant role in this patients group. The demyelination of vestibular neurons in the Ganglion Scarpae might be the cause of the Menière symptoms. To confirming the hypothesis, the research plan must be continuously carried out.

The role of theMelibebuccal ganglia in feeding behavior

A series of anatomical, physiological and behavioral experiments were conducted to determine the role of the Melibe buccal ganglia in feeding. The small, paired buccal ganglia are located on the surface of the esophagus, communicate with each other via a long buccal‐buccal connective, and with the brain via bilaterally symmetrical cerebral‐buccal connectives. They also innervate the anterior and posterior regions of the esophagus, and the paired salivary glands. Stimulation of the cerebral‐buccal connectives causes slow rhythmic contractions of the esophagus, and stimulation of either the anterior or posterior buccal nerves results in single contractions of the esophagus. Removal of both buccal ganglia does not impair the ability of animals to capture food, but it has a significant impact on the transfer of captured prey through the esophagus. These data, taken together, indicate that the Melibe buccal ganglia do not influence the capture of food, but rather control movements of the esophagus which are ne...

Mechanical Irritation Induces Neurogenic Inflammation in the Rat Urethra

A catheter was inserted into the urethral meatus of urethane-anaesthetized rats and rotated (30 rotations/minute) during a three minute period. One hour later, microvascular permeability in the distal urethra was evaluated by means of the Evans Blue leakage technique. Dye extravasation increased significantly (74 ± 12ng./mg. of wet tissue weight, p <0.05), as compared to control values (18 ± 2ng./mg.). The effect of catheterism was prevented by about 50% by systemic pretreatment with capsaicin performed in either adult or newborn rats, as well as by bilateral removal of pelvic ganglia. Furthermore, pretreatment with capsaicin of adult rats, combined to pelvic ganglionectomy, virtually abolished the inflammatory response produced by mechanical irritation of the urethra. These results indicate that: 1) the increase of vascular permeability produced by mechanical irritation is nerve-mediated, 2) capsaicin-sensitive afferents participate in the inflammatory process and 3) capsaicin-insensitive nerves, which pass through the pelvic ganglia, contribute to the overall response.

Ultrastructural organization of the interstitial subnucleus of the nucleus of the tractus solitarius in the cat: Identification of vagal afferents

This electron microscopic study, based on serial section analysis, describes the synaptic organization of the interstitial subnucleus of the nucleus of the solitary tract and identifies the terminals of the vagal primary afferents utilizing degeneration and HRP transport. The interstitial subnucleus contains sparsely scattered cell bodies, numerous dendrites and axon terminals, and bundles of unmyelinated and myelinated axons. The cell bodies which are small in diameter have an organelle poor cytoplasm and a large invaginated nucleus. Axon terminals can be classified into two main types according to their vesicular shape. The first type contains clear, round vesicles and can be further subdivided into two subgroups on the basis of their morphology and the size of their vesicles. In the first subgroup the terminals are small, contain a few mitochondria and their vesicles are densely packed with an homogeneous size. In the second subgroup the terminals which vary from small to large, contain many mitochondria and contain round vesicles which are heterogeneous in size. The second main terminal type consists of axon terminals containing pleomorphic vesicles which are associated with asymmetrical or symmetrical synaptic contacts on dendrites. Axo-axonic contacts are present in the interstitial subnucleus. In general, the presynaptic axon terminals contain pleomorphic vesicles and the postsynaptic elements contain round vesicles of varying size. In some dendrites, identified by the presence of ribosomes, groups of round and/or pleomorphic vesicles are found associated with synaptic contacts. These dendrites are presynaptic to conventional dendrites and postsynaptic to axon terminals. After removal of the nodose ganglion, degenerative alterations are seen only at the caudal and middle levels of the interstitial subnucleus. Degeneration occurs in a few myelinated axons and in axon terminals which usually contain a mixture of small and larger round, clear vesicles. After HRP injection into the vagus nerve, the HRP reaction product is visible in axon terminals filled with clear, round vesicles which are heterogeneous in size. The labelled axon terminals establish single or multiple synaptic contacts. This study demonstrates that terminals of vagal primary afferents consist principally of terminals of the second subgroup. The morphology of these terminals are compared to primary afferents in the brainstem and spinal cord.

Development and migration of avian sympathetic preganglionic neurons

Modern neuronanatomical techniques were used to investigate the development of the avian sympathetic preganglionic cell column in the spinal cord of the chick embryo. [3H]thymidine autoradiography indicated that the majority of these preganglionic, or "Terni column" neurons are generated between stages 18 and 24 (days 2-4). This coincides with the genesis of the somatic motoneurons in the thoracic levels of the cord, and therefore differences in the time of origin cannot explain the divergent fates of these two neuronal populations. Data obtained from short-survival autoradiographic experiments indicated that many early born cells remain close to the ventral region of the ventricular epithelium until day 5 of incubation. Ventral root injections used to label retrogradely neurons projecting an axon into the ventral root (Terni cells and somatic motoneurons) have labeled neurons next to the ventricular epithelium at the same early stages. Thus, it seems likely that some Terni cells, if not all, maintain medial positions and do not migrate laterally to join a common motor column before initiating a dorsal migration. Analysis of a closely staged series of embryos, whose Terni column neurons were retrogradely labeled with wheat germ agglutinin-horseradish peroxidase (WGA-HRP), revealed that between days 5 and 8 of incubation, Terni column neurons migrated dorsally to attain their adult position adjacent to the central canal. These changes in position were reflected in the changing morphology of the Terni column neurons, visualized by the Golgi-like HRP labeling. The positions of the migrating Terni cells differed from those of commissural cells, indicating that these fibers are not the substrate for the dorsal migration. The dorsal migration of Terni column cells was not disrupted by the surgical removal of the sympathetic ganglia, the synaptic targets of these neurons, nor by disruption of spinal afferents. Taken together, these results suggest that the migratory behavior of Terni cells in distinctive when compared to that of somatic motoneurons, and that local and/or intrinsic cues within the spinal cord guide the dorsal migration of Terni column cells.

Afferent innervation of the gallbladder in the cat, studied by the horseradish peroxidase method

Following injection of horseradish peroxidase (HRP) into the wall of the gallbladder of cats, HRP-positive cells were found bilaterally in dorsal root ganglia T2-L3 (T2-L2, and T3-L2/L3 also observed in a few cats) and nodose ganglia. In about 33% of animals labelled cells were also distributed in cervical dorsal root ganglia C5–C7. Labelled cells were more frequently localized on the right side than the left. There was no apparent change in numbers of labelled cells in the nodose ganglion (NG) on either side following greater and lesser splanchnicotomy or section of the right phrenic nerve or removal of the celiac ganglion. After severing both the greater and lesser splanchnic nerves unilaterally, numbers of labelled afferent cells from the gallbladder in dorsal root ganglia (DRGs) significantly decreased on the ipsilateral side but there was no change in the pattern of distribution contralaterally. After section of the right phrenic nerve, labelled cells were not found in ipsilateral cervical ganglia. That some afferent fibers from the gallbladder travel via the phrenic nerves, particularly on the right side, may be a supplementary mechanism in the generation of referred pain in gallbladder disease. The splanchnic nerves are the main, but not the only pathway for afferent fibers from the gallbladder.

Stimulatory and inhibitory cyclic AMP responses in rabbit ciliary processes after cervical ganglionectomy

Cyclic AMP production in response to agonists which act at a variety of receptors to either stimulate or inhibit cyclic AMP production has been studied in intact, dissected ciliary processes from rabbit eyes after unilateral surgical removal of the cervical ganglion. Cyclic AMP responses to stimulatory ligands vasoactive intestinal peptide (VIP), isoproterenol, and forskolin and inhibitory agonists neuropeptide Y (NPY), the synthetic somatostatin analogue SMS 201-995, and alpha-adrenergic agents were investigated in tissues from normal eyes and compared to the same responses in tissues from sympathetically denervated eyes. Neither stimulated cyclic AMP production nor inhibition of stimulated cyclic AMP production was significantly different in tissues from denervated vs. normal eyes. Inhibition of VIP-stimulated cyclic AMP production by epinephrine and paraaminoclonidine in tissues from both normal and denervated eyes was blocked by the alpha 2-adrenergic antagonist yohimbine but not by the alpha 1-adrenergic antagonist prazosin. These data indicate that the VIP, NPY, somatostatin, and alpha 2- and beta 2-adrenergic receptors which regulate cyclic AMP production in rabbit ciliary processes are postjunctional and suggest that ligands known to modulate cyclic AMP levels in this tissue may exert effects on aqueous humor formation independently of adrenergic innervation.

Plasticity of the sympathetic nerve fibers innervating the rat cerebral arteries after removal of the unilateral superior cervical ganglion

Plasticity of the sympathetic nerve fibers innervating the rat cerebral arteries after removal of the unilateral superior cervical ganglion

Ganglion causing paralysis of the suprascapular nerve: Diagnosis by MRI and ultrasonography

A 26-year-old man had a right infraspinatus muscle weakness and aching of the shoulder due to suprascapular nerve entrapment confirmed by electromyography. MRI revealed a well-defined area of increased signal intensity over the suprascapular notch. An ultrasonogram showed a homogeneous hypoechogenic area at the base of the scapular spine. A diagnosis was made of a ganglion compressing the inferior branch of the suprascapular nerve. After removal of several ganglia, the patient had immediate pain relief, and normal electromyographic findings were obtained 5 months postoperatively.

Protein Phosphorylation in Intact Superior Cervical Ganglion During Regeneration

The incorporation of radioactive phosphate into proteins of both normal and regenerating superior cervical ganglion nerve of the rat is reported. Incorporation studies carried out by in vitro and in vivo methods are compared. In the in vitro method, excised intact ganglia or their homogenates were incubated in the presence of inorganic phosphate or ATP, respectively, under various conditions. Proteins were analyzed by gel electrophoresis followed by autoradiography, in which quantitative but not qualitative differences between regenerating and control cases were apparent. In the in vivo procedure, inorganic phosphate was injected into the living animal 4 h before removal of ganglia. At least fivefold more proteins became labeled in vivo than in vitro, whereas no similarity in the pattern of labeling between the two methods was observed. For example, the most heavily labeled protein in the in vivo method, tentatively identified as microtubule-associated protein-2, was not detected on autoradiograms of proteins labeled by the in vitro method. In this latter method, an 85-kDa species and growth-associated protein-43 were always labeled, and the extent of their phosphorylation was enhanced by the additional presence of phosphatidylserine and Ca2+, a result indicating that these labeled species are substrates of protein kinase C. The in vitro conditions also led to the labeling of proteins identified as alpha- and beta-tubulin. Comparison of the methods suggests that removal of the ganglion interferes with the function of protein phosphorylation systems and that this effect involves elements of the cytoskeleton.

Neural influences on synovial mast cell density in rat

The mast cell, an immunocompetent cell that contributes to neurogenic inflammation in a variety of tissues, including synovium, is found in close proximity to peripheral terminals of unmyelinated primary afferents and sympathetic postganglionic nerve terminals. In this study we evaluated the hypothesis that the density of mast cells in synovial tissue is dependent on the neural innervation. In normal rats, we found that the density of mast cells in the ankle joint capsule, which is heavily innervated, is greater than in the capsule of the knee, which is less densely innervated. Selective lesions of unmyelinated primary afferents with capsaicin, or of sympathetic postganglionic neurons with guanethidine, produced a significant decrease in mast cells; surgical removal of the parasympathetic ganglia did not significantly affect mast cell density. Finally, the number of mast cells in the synovial joint of spontaneously hypertensive rats, which have increased sympathetic activity, was significantly greater than in normotensive control rats. These observations support the hypothesis that the innervation in the synovial joint of the rat, by unmyelinated afferents and sympathetic efferents, exerts a trophic effect on mast cell density.

Evidence that toluene diisocyanate activates the efferent function of capsaicin-sensitive primary afferents

Isocyanates are an important cause of occupational asthma. The mechanism of isocyanate-induced asthma is still unknown. To determine whether toluene diisocyanate stimulates the ‘efferent’ function of peripheral endings of capsaicin-sensitive sensory nerves, we investigated the effect of toluene diisocyanate in the rat isolated urinary bladder, a preparation in which the action of capsaicin has been well characterized. Toluene diisocyanate (0.03–3 mM) produced a concentration-dependent contraction of the bladder strips. Its maximal effect was about 50% of the response to capsaicin (1 μM). Previous exposure of the strips to capsaicin followed by washing out produced complete unresponsiveness, both to the first exposure to toluene diisocyanate and to a second exposure of capsaicin. Further, the response to both toluene diisocyanate and capsaicin was completely prevented by extrinsic bladder denervation, achieved by bilateral removal of pelvic ganglia (72 h before). Repeated exposure of the rat bladder to toluene diisocyanate reduced the capsaicin-evoked release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI), taken as biochemical marker of activation of these sensory nerves. These experiments provide the first evidence that toluene diisocyanate activates directly or indirectly the efferent function of capsaicin-sensitive primary sensory nerves.