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At least 19 recordsLinked to original sources
PubMed1989

[Localization of efferent sympathetic neurons and afferent neurons in dorsal root ganglia innervating the heart].

The retrograde transport of horseradish peroxidase (HRP) has been used to study the localization and the number of neurons innervating the heart in the right stellate ganglion and accessory cervical ganglion, spinal cord and dorsal root ganglia of the cat. HRP was applied to the central cuts of anastomose of the stellate ganglion with the vagal nerve, of the vagosympathetic trunk caudal to anastomose and of the inferior cardiac nerve. HRP-labelled neurons were detected in the stellate ganglion in the regions which give off nerves, whereas in the accessory cervical ganglion labelled neurons were distributed throughout the whole ganglion. HRP-stained cells were found in the anastomose. In the spinal cord labelled neurons were detected in the lateral horn of T1-T5 segments. In the dorsal root ganglion the greatest number of neurons was observed in T2-T4 segments.

Animals↗
PubMed2005

Primary afferent neurons intrinsic to the guinea-pig intestine, like primary afferent neurons of spinal and cranial sensory ganglia, bind the lectin, IB4.

The plant lectin, IB4, binds to the surfaces of primary afferent neurons of the dorsal root and trigeminal ganglia and is documented to be selective for nociceptive neurons. Physiological data suggest that the intrinsic primary afferent neurons within the intestine are also nociceptors. In this study, we have compared IB4 binding to each of these neuron types in the guinea-pig. The only neurons in the intestine to be readily revealed by IB4 binding have Dogiel-type-II morphology; these neurons have been previously identified as intrinsic primary afferent neurons. Most of the neurons that are IB4-positive in the myenteric plexus are calbindin-immunoreactive, whereas those in the submucosal ganglia are immunoreactive for NeuN. The neurons that bind IB4 strongly have a similar appearance in enteric, dorsal root and trigeminal ganglia. Binding is to the cell surface, to the first part of axons and to cytoplasmic organelles. A low level of binding was found in the extracellular matrix. A few other neurons in all ganglia exhibit faint staining with IB4. Strongly reactive neurons are absent from the gastric corpus. Thus, IB4 binding reveals primary afferent neurons with similar morphologies, patterns of binding and physiological roles in enteric, dorsal root and trigeminal ganglia.

Animals↗
PubMed2002

Prevertebral ganglia and intestinofugal afferent neurones.

Intestinofugal afferent neurones (IFANs) are a unique subset of myenteric ganglion neurones that regulate normal gastrointestinal function. The IFANs relaying mechanosensory information to sympathetic neurones of the prevertebral ganglion (PVG) function as volume detectors. It is possible that mechanosensory information arriving in the PVG via axon collaterals of visceral spinal afferent nerves can be modulated entirely within the PVG itself.

Ganglia, Autonomic↗
PubMed2004

Calcitonin gene-related peptide regulates gene transcription in primary afferent neurons.

Although primary afferent neurons express receptors for calcitonin gene-related peptide (CGRP), understanding of the cellular effects of these receptors is limited. We determined that CGRP receptors regulate gene transcription in primary afferent neurons through a cyclic AMP (cAMP)-dependent pathway. CGRP increased cAMP in neonatal dorsal root ganglion (DRG) neurons in a concentration-dependent manner that was blocked by the receptor antagonist CGRP(8-37). The response to CGRP also occurred in adult DRG cells. In contrast, CGRP did not alter the concentration of free intracellular calcium in neonatal or adult DRG neurons. Immunohistochemical data showed that one downstream effect of the cAMP signaling pathway was phosphorylation of cAMP response element binding (CREB) protein, suggesting that CGRP regulates gene expression. This interpretation was supported by evidence that CGRP increased CRE-dependent gene transcription in neurons transiently transfected with a CRE-luciferase DNA reporter construct. The effect of CGRP on gene transcription was inhibited by H89, myristoylated-protein kinase A inhibitor(14-22)-amide and U0126, indicating that protein kinase A and mitogen-activated protein kinase/extracellular receptor kinase kinase are enzymes that mediate effects of CGRP on gene transcription. Therefore, CGRP receptors may regulate expression of proteins by primary afferent neurons during development and in response to tissue-damaging stimuli.

Aging↗
PubMed1996

Interactions of sympathetic and primary afferent neurons following nerve injury and tissue trauma.

Sympathetic post-ganglionic neurons may be involved in the generation of pain, hyperalgesia and inflammation under pathophysiological conditions. Two categories of influence of the sympathetic neuron on afferent neurons can be distinguished and this distinction seems to be related to whether the coupling between afferent and sympathetic neuron develops after nerve lesion or after tissue trauma with inflammation (Fig. 15): A. Peripheral nerve lesion generates plastic changes of the afferent and sympathetic postganglionic neurons, depending on the type of nerve lesion (e.g. complete, partial). Both afferent and post-ganglionic neurons exhibit degenerative and regenerative changes and unlesioned neurons may show collateral sprouting in the periphery as well as in the dorsal root ganglion. This reorganization of the peripheral neurons may lead to chemical coupling between sympathetic and afferent neurons. The coupling is responsible for sensitization and/or activation of primary afferent neurons by the sympathetic neurons. The mediator probably is norepinephrine, but other substances cannot be excluded. The afferent neuron expresses or upregulates functional adrenoceptors. The type of adrenoceptor involved is probably alpha 2. The coupling may occur at different sites of the primary afferent neuron, e.g. at the lesion site, remote from the lesion site in the dorsal root ganglion or between nonlesioned sympathetic and afferent neurons which show collateral sprouting. The biochemical signals which trigger these changes probably are neurotrophic substances, their receptors which are synthesized by the peripheral neurons, Schwann cells and other cells in response to the peripheral lesions. B. Sympathetic nerve terminals in peripheral tissues may serve as mediator elements in hyperalgesia and inflammation following tissue trauma without nerve lesion. Experiments show that these functions are largely independent of activity in the sympathetic neurons and independent of vesicular release of transmitter substances (such as norepinephrine). Sensitization of nociceptive afferents for mechanical stimuli and venular plasma extravasation in the synovium which are induced by the inflammatory mediator bradykinin are, at least in part, dependent on the sympathetic terminal. The signal to venules and afferent receptors is synthesized and released from the sympathetic terminal or in association with it. It is a prostaglandin (probably PGE2). Sympathetically mediated (neurogenic) inflammation and neurogenic inflammation mediated by afferents may interact reciprocally and enhance the inflammatory process as well as the sensitization of nociceptive afferents. Norepinephrine may also lead to sensitization of nociceptive afferents under inflammatory conditions. This sensitization is presumably mediated by alpha 2-adrenoceptors in the sympathetic varicosities and by a prostaglandin (probably PGI2) which is synthesized and released by or in association with the sympathetic varicosities.

Extremities↗
PubMed2002

The study of airway primary afferent neuron excitability.

The activation of airway afferent neurons initiates a variety of reflexes including cough and bronchoconstriction. Like somatic afferent neurons involved in inflammation-induced hyperalgesia, the excitability of airway afferent neurons is not fixed but, rather, can be increased by the action of a variety of mediators produced during inflammation. A variety of techniques have been applied to study the pharmacological modulation of the excitability of afferent neurons. Although airway afferent neurons have not been studied to the same extent as fibers involved in hyperalgesia, similar pathways may control their excitability. The ability to study the pharmacological modulation of airway afferent neuron excitability is crucial to our understanding of airway afferent neurophysiology and may also provide insight into novel therapeutic targets for various inflammatory lung diseases.

Animals↗
PubMed2000

Neurotrophins alter the numbers of neurotransmitter-ir mature vagal/glossopharyngeal visceral afferent neurons in vitro.

Mature nodose and petrosal ganglia neurons (placodally derived afferent neurons of the vagal and glossopharyngeal nerves) contain TrkA and TrkC, and transport specific neurotrophins [nerve growth factor (NGF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4)]. This study evaluated neurotrophin influences on the presence of neuropeptides and/or neurotransmitter enzymes in these visceral sensory neurons. NGF, NT-3 and NT-4 (10-100 ng/ml) were applied (5 days) to dissociated, enriched, cultures of mature nodose/petrosal ganglia neurons, and the neurons processed for tyrosine hydroxylase (TH), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and neurofilament (NF-200) immunocytochemistry. Addition of NGF to nodose/petrosal ganglia neuron-enriched cultures significantly increased the number of TH-immunoreactive (ir) neurons, decreased the number of VIP-ir neurons in the cultures, and did not affect the numbers of CGRP-ir neurons. The addition of an NGF neutralizing antibody attenuated the effects of NGF on TH and VIP-ir neurons. NT-3 increased the number of VIP-ir neurons in the nodose/petrosal ganglia cultures and did not alter the numbers of TH-, or CGRP-ir neurons. The addition of an NT-3 neutralizing antibody attenuated the effects of NT-3 on VIP-ir neurons. NT-4 had no significant effects on the numbers of TH, VIP and CGRP-ir neurons. The absence of neurotrophin-induced changes in the numbers of NF-200-ir neurons in culture showed the lack of neurotrophin-mediated changes in survival of mature vagal afferent neurons. These data demonstrate that specific neurotrophins influence the numbers of neurons labeled for specific neurochemicals in nodose/petrosal ganglia cultures. These data, coupled with previous evidence for the presence of TrkA and TrkC mRNA and of the retrograde transport of NGF and NT-3, suggest important roles for NGF and NT-3 in the maintenance of transmitter phenotype of these mature visceral afferent neurons.

Age Factors↗
PubMed1990

Morphine potentiation of ethanol-induced gastric mucosal damage in the rat. Role of local sensory afferent neurons.

Local capsaicin-sensitive sensory afferent neurons may regulate the ability of the gastric mucosa to withstand challenge. Since opioids can modulate the activity of afferent neurones by actions at peripheral sites, the effects of morphine on gastric mucosal damage has been investigated in the rat. Morphine (3-9 mg.kg-1 i.v.) dose-dependently augmented the damage induced by a 5-min intragastric challenge with ethanol (25%-100%), as assessed by macroscopic and histological evaluation. These effects of morphine were significantly inhibited by the opioid antagonists naloxone and the peripherally acting N-methylnalorphine. Pretreatment of rats with capsaicin 2 weeks before the study to induce functional ablation of primary afferent neurons likewise significantly augmented the damage induced by ethanol. Both morphine administration and capsaicin pretreatment substantially augmented histologically assessed damage to the glandular mucosa and enhanced deep hemorrhagic damage following challenge with the low ethanol concentrations, with the appearance of macroscopically distinct antral damage. The enhanced damage induced by 50% ethanol in capsaicin-pretreated rats was not further enhanced by morphine administration, suggesting actions on a common mechanism. These findings support a pathophysiological role for activation of local opioid-sensitive afferent neurons in the modulation of mucosal injury following challenge.

Animals↗
PubMed1998

Intrinsic primary afferent neurons of the intestine.

After a long period of inconclusive observations, the intrinsic primary afferent neurons of the intestine have been identified. The intestine is thus equipped with two groups of afferent neurons, those with cell bodies in cranial and dorsal root ganglia, and these recently identified afferent neurons with cell bodies in the wall of the intestine. The first, tentative, identification of intrinsic primary afferent neurons was by their morphology, which is type II in the terminology of Dogiel. These are multipolar neurons, with some axons that project to other nerve cells in the intestine and other axons that project to the mucosa. Definitive identification came only recently when action potentials were recorded intracellularly from Dogiel type II neurons in response to chemicals applied to the lumenal surface of the intestine and in response to tension in the muscle. These action potentials persisted after all synaptic transmission was blocked, proving the Dogiel type II neurons to be primary afferent neurons. Less direct evidence indicates that intrinsic primary afferent neurons that respond to mechanical stimulation of the mucosal lining are also Dogiel type II neurons. Electrophysiologically, the Dogiel type II neurons are referred to as AH neurons. They exhibit broad action potentials that are followed by early and late afterhyperpolarizing potentials. The intrinsic primary afferent neurons connect with each other at synapses where they transmit via slow excitatory postsynaptic potentials, that last for tens of seconds. Thus the intrinsic primary afferent neurons form self-reinforcing networks. The slow excitatory postsynaptic potentials counteract the late afterhyperpolarizing potentials, thereby increasing the period during which the cells can fire action potentials at high rates. Intrinsic primary afferent neurons transmit to second order neurons (interneurons and motor neurons) via both slow and fast excitatory postsynaptic potentials. Excitation of the intrinsic primary afferent neurons by lumenal chemicals or mechanical stimulation of the mucosa appears to be indirect, via the release of active compounds from endocrine cells in the epithelium. Stretch-induced activation of the intrinsic primary afferent neurons is at least partly dependent on tension generation in smooth muscle, that is itself sensitive to stretch. The intrinsic primary afferent neurons of the intestine are the only vertebrate primary afferent neurons so far identified with cell bodies in a peripheral organ. They are multipolar and receive synapses on their cell bodies, unlike cranial and spinal primary afferent neurons. They communicate with each other via slow excitatory synaptic potentials in self reinforcing networks and with interneurons and motor neurons via both fast and slow EPSPs.

Animals↗
PubMed1996

GABAA-receptor-mediated conductance and action potential waveform in cutaneous and muscle afferent neurons of the adult rat: differential expression and response to nerve injury.

1. Whole cell patch-clamp recordings were obtained from identified cutaneous and muscle afferent neurons (33-60 microns diam) in dissociated L4 and L5 dorsal root ganglia (DRGs) from normal rats and from rats 2-3 wk after sciatic nerve ligation or crush injury. gamma-Aminobutyric acid (GABA)-induced conductance was compared in normal and injured neurons from both functional classes of sensory neurons. 2. Control cutaneous afferent neurons had a peak GABA-mediated conductance of 287 +/- 27 (SE) nS compared with 457 +/- 42 nS for control muscle afferent neurons. 3. An inflection on the downslope of the action potential was observed in 47% of cutaneous afferent neurons compared with 20% of muscle afferent neurons. 4. After ligation and transection of the sciatic nerve there was no change in the GABA-mediated conductance of muscle afferent neurons or in the action potential waveform (23% inflected). However, the cutaneous afferent neurons displayed a greater than two-fold increase in their GABA-mediated conductance and displayed a prominent reduction in the number of neurons with inflected action potentials (13% inflected). Input resistance was similar in cutaneous and muscle afferent neurons and decreased after ligation in cutaneous but not muscle afferents. Resting potential averaged from -50 to -56 mV in normal and ligated groups for both cutaneous and muscle afferent neurons. 5. After crush injury in cutaneous afferent neurons where the transected axons were allowed to regenerate into the distal nerve stump, GABAA-receptor-mediated conductance was elevated compared with controls. However, action potential waveform was not altered by crush injury, suggesting a differential regulation of these two properties in cutaneous afferent neurons. 6. These data indicate that injury-induced plasticity of GABAA-receptor-mediated conductance and action potential waveform occurs in cutaneous but not muscle afferent DRG neurons. It appears that peripherally derived influences are critical in maintaining the electrophysiological phenotype of cutaneous afferent neurons but not muscle afferent neurons.

Action Potentials↗
PubMed2001

Transduction capabilities of neonatal ventricular afferent neurons in vivo.

We sought to determine the capacity of ventricular sensory nerve endings (neurites) associated with neonatal nodose ganglion afferent neurons to transduce mechanical and chemical stimuli in situ. Spontaneous activity generated by 17 nodose ganglion cardiac afferent neurons was identified in 8 anesthetized neonatal pigs (10-21 days old) using extracellular recording recording techniques. The activity generated by afferent neurons was studied when their ventricular sensory neurites were exposed to local mechanical or chemical stimuli, following systemic administration of specific chemicals or during brief periods of apnea. Gentle mechanical distortion of their ventricular sensory fields enhanced the activity generated by 6 spontaneously active afferent neurons, while suppressing the activity generated by another 3 neurons. Afferent neuronal activity was either enhanced or suppressed when the following chemicals were applied to identified ventricular epicardial sensory fields: the sodium channel modifier veratridine (92% of tested neurons); the P1-purinoceptor agonist adenosine (92%); the neuropeptides angiotensin II (100%), bradykinin (90%) and substance P (90%); and the nitric oxide donor S-nitroso-N-acetylpenicillamine (100%). Epicardial application of isoproternol or nicotine induced modest neuronal responses. Cardiac afferent neurons were also affected when these chemicals were administered systemically. Apnea of 60-100 s duration modified (enhanced, n = 2; suppressed, n = 5) the activity generated by most identified afferent neurons. The estimated average conduction velocity of afferent axons associated with these neurons was 1.0 +/- 0.2 m/s. It is concluded that neonatal nodose ganglion cardiac afferent neurons respond to many of the chemicals known to modify adult cardiac afferent neurons. That cardiac afferent neurons are capable of sensing the mechanical and chemical milieu of the neonatal heart should be taken into account when considering altered neonatal cardiovascular status such as occurs during apnea.

Action Potentials↗
PubMed2003

Chemical phenotypes of muscle and cutaneous afferent neurons in the rat trigeminal ganglion.

Retrograde labeling was combined with cytochemistry to investigate phenotypic differences in primary afferent neurons relaying sensory information from deep and superficial craniofacial tissues. Calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM) immunoreactivity and isolectin IB4, and cholera toxin B (ChTB) binding were examined for trigeminal masticatory muscle and cutaneous afferent neurons. Somata labeled from muscle were larger than cutaneous afferent neurons. Muscle afferent neurons exhibited positive staining as follows: 22% CGRP, 5% SP, 0% SOM; 18% ChTB, 5% IB4. The somata of CGRP- and SP-positive muscle afferent neurons were smaller than that of the overall muscle afferent population. Size differences were not detected between IB4- or ChTB-binding muscle afferent neurons and the total muscle afferent population. The following distribution was found for cutaneous afferent neurons: 26% CGRP, 7% SP, 1% SOM, 26% ChTB, 44% IB4. Cutaneous afferent neurons positive for SP were smaller, while ChTB-binding cutaneous afferents were larger than the overall cutaneous afferent population. No size differences were found between cutaneous CGRP-, SOM-, or IB4-positive neurons and the total cutaneous afferent population. Target-specific differences exist for SOM and IB4. The percentage of cutaneous afferent neurons positive for SOM and IB4 exceeds that for SOM- or IB4-positive muscle afferents. The number of retrogradely labeled neurons never differed between sexes. The percentage of retrogradely labeled muscle afferent neurons that were CGRP-positive was greater in males than females. These data indicate the presence of phenotypic, target, and sex differences in trigeminal ganglion primary afferent neurons.

Animals↗
PubMed2005

Ca2+-activated K+-current density is correlated with soma size in rat vestibular-afferent neurons in culture.

Vestibular-afferent neurons (VANs) transmit information about linear and angular accelerations during head movements from vestibular end organs to vestibular nuclei. In situ, these neurons show heterogeneous discharge patterns that may be produced by differences in their intrinsic properties. However, little is known about the ionic currents underlying their different firing patterns. Using the whole cell patch-clamp technique, we analyzed the expression of Ca(2+) and Ca(2+)-activated K(+) currents (I(KCa)) in primary cultured neurons isolated from young rats (p7-p10). We found two overlapping subpopulations of VANs classified according to low-threshold Ca(2+)-current [low-voltage-activated (LVA)] expression; LVA (-) neurons, formed by small cells, and LVA (+) neurons composed of medium to large cells. The I(KCa) in both cell-groups was carried through channels of high (BK), intermediate (IK), and low conductance (SK), besides a resistant channel to classical blockers (IR). BK was expressed preferentially in LVA (+) cells, whereas IR expression was preferentially in LVA (-) cells. No correlation between SK and IK expression with the soma size was found. Current-clamp experiments showed that BK participates in the adaptation of discharge and in the duration of the action potential, whereas SK and IK did not show a significant contribution to electrical discharge of cultured VANs. However, because of the low number of VANs in culture with repetitive firing it is difficult to interpret our results in terms of discharge patterns. Our results demonstrate that vestibular-afferent neurons possess different Ca(2+)-activated K(+) (K(Ca)) channels and that their expression, heterogeneous among the cells, would contribute to explain some of the differences in the electrical-firing properties of these neurons.

4-Aminopyridine↗
PubMed2003

Tetrodotoxin-resistant sodium channels Na(v)1.8/SNS and Na(v)1.9/NaN in afferent neurons innervating urinary bladder in control and spinal cord injured rats.

Tetrodotoxin-resistant (TTX-R) sodium channels Na(v)1.8/SNS and Na(v)1.9/NaN are preferentially expressed in small diameter dorsal root ganglia (DRG) neurons. The urinary bladder is innervated by small afferent neurons from L6/S1 DRG, of which approximately 75% exhibit high-threshold action potentials that are mediated by TTX-R sodium channels. Following transection of the spinal cord at T8, the bladder becomes areflexic and then gradually hyper-reflexic, and there is an attenuation of the TTX-R sodium currents in bladder afferent neurons. In the present study, we demonstrate that Na(v)1.8 is expressed in both bladder and non-bladder afferent neurons, while Na(v)1.9 is expressed in non-bladder afferent neurons but is rarely observed in bladder afferent neurons. In spinal cord transected rats 28-32 days following transection, there is a decreased expression of Na(v)1.8 sodium channels in bladder afferents, but no change in the expression of Na(v)1.8 in non-bladder afferent neurons. Both bladder and non-bladder afferent neurons exhibit limited increases in Na(v)1.9 expression following spinal cord transection. These results demonstrate that the expression of TTX-R channels in bladder afferent neurons changes after spinal cord transection, and these changes may contribute to the increased excitability of these neurons following spinal cord injury.

Animals↗
PubMed1999

Increased excitability of afferent neurons innervating rat urinary bladder after chronic bladder inflammation.

The properties of bladder afferent neurons in L6 and S1 dorsal root ganglia of adult rats were evaluated after chronic bladder inflammation induced by 2 week treatment with cyclophosphamide (CYP; 75 mg/kg). Whole-cell patch-clamp recordings revealed that most (70%) of the dissociated bladder afferent neurons from control rats were capsaicin sensitive, with high-threshold long-duration action potentials that were not blocked by tetrodotoxin (TTX; 1 microM). These neurons exhibited membrane potential relaxations during voltage responses elicited by depolarizing current pulses and phasic firing during sustained membrane depolarization. After CYP treatment, a similar proportion (71%) of bladder afferent neurons were capsaicin sensitive with TTX-resistant spikes. However, the neurons were significantly larger in size (diameter 29.6 +/- 1.0 micrometer vs 23.6 +/- 0.8 micrometer in controls). TTX-resistant bladder afferent neurons from CYP-treated rats exhibited lower thresholds for spike activation (-25.4 +/- 0.5 mV) than those from control rats (-21.4 +/- 0.9 mV) and did not exhibit membrane potential relaxation during depolarization. Seventy percent of TTX-resistant bladder afferent neurons from CYP-treated rats exhibited tonic firing (average 12.3 +/- 1.4 spikes during a 500 msec depolarizing pulse) versus phasic firing (1.2 +/- 0.2 spikes) in normal bladder afferent neurons. Application of 4-aminopyridine (1 mM) to normal TTX-resistant bladder afferent neurons mimicked the changes in firing properties after CYP treatment. The peak density of an A-type K+ current (IA) during depolarizations to 0 mV in TTX-resistant bladder afferent neurons from CYP-treated rats was significantly smaller (42.9 pA/pF) than that from control rats (109.4 pA/pF), and the inactivation curve of the IA current was displaced to more hyperpolarized levels by approximately 15 mV after CYP treatment. These data suggest that chronic inflammation induces somal hypertrophy and increases the excitability of C-fiber bladder afferent neurons by suppressing IA channels. Similar electrical changes in sensory pathways may contribute to cystitis-induced pain and hyperactivity of the bladder.

4-Aminopyridine↗
PubMed2002

Cannabinoids attenuate depolarization-dependent Ca2+ influx in intermediate-size primary afferent neurons of adult rats.

CB1 receptors have been localized to primary afferent neurons, but little is known about the direct effect of cannabinoids on these neurons. The depolarization-evoked increase in the concentration of free intracellular calcium ([Ca(2+)](i)), measured by microfluorimetry, was used as a bioassay for the effect of cannabinoids on isolated, adult rat primary afferent neurons 20-28 h after dissociation of dorsal root ganglia. Cannabinoid agonists CP 55,940 (100 nM) and WIN 55,212-2 (1 microM) had no effect on the mean K(+)-evoked increase in [Ca(2+)](i) in neurons with a somal area<800 microm(2), but the ligands attenuated the evoked increase in [Ca(2+)](i) by 35% in neurons defined as intermediate in size (800-1500 microm(2)). The effects of CP 55,940 and WIN 55,212-2 were mediated by the CB1 receptor on the basis of relative effective concentrations, blockade by the CB1 receptor antagonist SR141716A and lack of effect of WIN 55,212-3. Intermediate-size neurons rarely responded to capsaicin (100 nM). Although cannabinoid agonists generally did not inhibit depolarization-evoked increases in [Ca(2+)](i) in small neurons, immunocytochemical studies indicated that CB1 receptor-immunoreactivity occurred in this population. CB1 receptor-immunoreactive neurons ranged in size from 227 to 2995 microm(2) (mean somal area of 1044 microm(2)). In double labeling studies, CB1 receptor-immunoreactivity co-localized with labeling for calcitonin gene-related peptide and RT97, a marker for myelination, in some primary afferent neurons. The decrease in evoked Ca(2+) influx indicates that cannabinoids decrease conductance through voltage-dependent calcium channels in a subpopulation of primary afferent neurons. Modulation of calcium channels is one mechanism by which cannabinoids may decrease transmitter release from primary afferent neurons. An effect on voltage-dependent calcium channels, however, represents only one possible effect of cannabinoids on primary afferent neurons. Identifying the mechanisms by which cannabinoids modulate nociceptive neurons will increase our understanding of how cannabinoids produce anti-nociception in normal animals and animals with tissue injury.

Age Factors↗
PubMed2000

Painful neuropathy decreases membrane calcium current in mammalian primary afferent neurons.

Hyperexcitability of the primary afferent neuron leads to neuropathic pain following injury to peripheral axons. Changes in calcium channel function of sensory neurons following injury have not been directly examined at the channel level, even though calcium is a primary second messenger-regulating neuronal function. We compared calcium currents (I(Ca)) in 101 acutely isolated dorsal root ganglion neurons from 31 rats with neuropathic pain following chronic constriction injury (CCI) of the sciatic nerve, to cells from 25 rats with normal sensory function following sham surgery. Cells projecting to the sciatic nerve were identified with a fluorescent label applied at the CCI site. Membrane function was determined using patch-clamp techniques in current clamp mode, and in voltage-clamp mode using solutions and conditions designed to isolate I(Ca). Somata of peripheral sensory neurons from hyperalgesic rats demonstrated decreased I(Ca). Peak calcium channel current density was diminished by injury from 3.06+/-0.30 pS/pF to 2. 22+/-0.26 pS/pF in medium neurons, and from 3.93+/-0.38 pS/pF to 2. 99+/-0.40 pS/pF in large neurons. Under these voltage and pharmacologic conditions, medium-sized neuropathic cells lacked obvious T-type calcium currents which were present in 25% of medium-sized cells from control animals. Altered Ca(2+) signalling in injured sensory neurons may contribute to hyperexcitability leading to neuropathic pain.

Action Potentials↗
PubMed2006

Novel gut afferents: Intrinsic afferent neurons and intestinofugal neurons.

Information about the conditions of all tissues in the body is conveyed to the central nervous system through afferent neurons. Uniquely amongst peripheral organs, the intestine has numerous additional afferent neurons, intrinsic primary afferent neurons that have their cell bodies and processes in the enteric plexuses and do not project to the central nervous system. They detect conditions within the gut and convey that information to intrinsic reflex pathways that are also entirely contained inside the gut wall. Intrinsic primary afferent neurons respond both to the presence of material in the gut lumen and to distension of the gut wall and initiate reflex changes in contractile activity, fluid transport across the mucosa and local blood flow. They also function as nociceptors that initiate tissue-protective propulsive and secretory reflexes to rid the gut of pathogens. The regulation of excitability of intrinsic primary afferent neurons is through multiple ion channels and ion channel regulators, and their excitability is critical to setting the strength of enteric reflexes. The intestine also provides afferent signals to sympathetic pre-vertebral ganglia. The signals are conveyed from the gut by intestinofugal neurons that have their cell bodies within enteric ganglia and form synapses in the sympathetic ganglia. Intestinofugal neurons form parts of the afferent limbs of entero-enteric inhibitory reflexes. Because the unusual afferent neurons of the small intestine and colon make their synaptic connections outside the central nervous system, the neurons and the reflex centres that they affect are potential targets for non-central penetrant therapeutic compounds.

Animals↗