Mixed Nerve Stimulation Research Articles

Protective effect of a new hypothalamic peptide against cobra venom and trauma-induced neuronal injury.

A study of separate and combined actions of cobra venom (CV) and a new hypothalamic proline-rich polypeptide (PRP) isolated from magnocellular cells (NPV and NSO) on intoxication- and trauma-induced neuronal injury (during 3-4 weeks after hemisection with and without PRP treatment) was carried out. The registration of background and evoked impulse activity flow, changes in spinal cord (SC) inter- and motoneurons, responding to flexor, extensor, and mixed nerve stimulation in both acute and chronic experimental neurodegeneration was performed. The facilitating effect of PRP on the abovementioned neurons was revealed. High doses of CV that evoked the neurodegenerative changes demonstrated an inhibitory effect. In this case PRP treatment both before and after intoxication restored electrical neuronal activity to baseline level and higher. These results are evidence of protective action of PRP. The low doses of CV induced a facilitating effect. The combination of CV and PRP displayed an additive facilitating effect; in a number of cases the repeated administration of CV led to decrease of significant PRP effect till baseline level (for example, the inhibition after primary response prior to secondary late discharge). Greater liability of the secondary early and late long-time discharges of poststimulus responses, differently expressed in various neuron types of SC to chemical influences is of interest. PRP-induced inhibition of the paroxysmal activity related with CV action is also very interesting. Morpho-functional experiments with SC injury demonstrated the abolition of difference in the background and evoked SC neuronal activity below the section and on intact symmetric side after daily PRP administration for 3 weeks. PRP hindered the scar formation and activated neuroglia proliferation; it promoted white matter element growth, hampered the degeneration of cellular elements, and protected against tissue stress. Our results favor the combined use of PRP and CV in clinical practice for the treatment of neurodegeneration of toxic and traumatic origin, as well as specific neurodegenerative diseases such as Alzheimer's.

The excitability of human cortical inhibitory circuits responsible for the muscle silent period after transcranial brain stimulation.

The silent period after transcranial magnetic brain stimulation mainly reflects the activity of inhibitory circuits in the human motor cortex. To assess the excitability of the cortical inhibitory mechanisms responsible for the silent period after transcranial stimulation, we studied, in 15 healthy human subjects, the recovery cycle of the silent period evoked by transcranial and mixed nerve stimulation delivered with a paired stimulation technique. The recovery cycle is defined as the time course of the changes in the size or duration of a conditioned test response when pairs of stimuli (conditioning and test) are used at different conditioning-test intervals. The recovery cycle of the duration of the silent period in the first dorsal interosseous (FDI) muscle during maximum voluntary contraction after transcranial magnetic stimulation was studied by delivering paired magnetic shocks (a conditioning shock and a test shock) at 120% motor-threshold intensity. Conditioning-test intervals ranged from 20-550 ms. The recovery cycle of the silent period in the FDI muscle during maximum voluntary contraction after nerve stimulation was evaluated by paired, supramaximum bipolar electrical stimulation of the ulnar nerve at the wrist (conditioning-test intervals ranging from 20 to 550 ms). Electromyographic activity was recorded by a pair of surface-disk electrodes over the FDI muscle. The recovery cycle of the silent period after transcranial magnetic stimulation delivered through the large round coil showed two phases of facilitation (lengthening of the silent period), one at 20-40 ms and the other at 180-350 ms conditioning-test intervals, with an interposed phase of inhibition (shortening of the silent period) at 80-160 ms. The conditioning magnetic shock left the size of the test motor-evoked potentials statistically unchanged during maximum voluntary contraction. Paired transcranial stimulation with a figure-of-eight coil increased the duration of the test silent period only at short conditioning-test intervals. Conditioning nerve stimulation left the silent period produced by test nerve stimulation unchanged. In conclusion, after a single transcranial magnetic shock, inhibitory circuits in the human motor cortex undergo distinctive short-term changes in their excitability, probably involving different mechanisms.

Changes in muscle responses to stimulation of the motor cortex induced by peripheral nerve stimulation in human subjects.

The aim of this study was to determine whether prolonged, repetitive mixed nerve stimulation (duty cycle 1 s, 500 ms on-500 ms off, 10 Hz) of the ulnar nerve leads to a change in excitability of primary motor cortex in normal human subjects. Motor-evoked potentials (MEPs) generated in three intrinsic hand muscles [abductor digiti minimi (ADM), first dorsal interosseous (FDI) and abductor pollicis brevis (APB)] by focal transcranial magnetic stimulation were recorded during complete relaxation before and after a period of prolonged repetitive ulnar nerve stimulation at the wrist. Transcranial magnetic stimuli were applied at seven scalp sites separated by 1 cm: the optimal scalp site for eliciting MEPs in the target muscle (FDI), three sites medial to the optimal site and three sites lateral to the optimal stimulation site. The area of the MEPs evoked in the ulnar-(FDI, ADM) but not the median-innervated (APB) muscles was increased after prolonged ulnar nerve stimulation. Centre of gravity measures demonstrated that there was no significant difference in the distribution of cortical excitability after the peripheral stimulation. F-wave responses in the intrinsic hand muscles were not altered after prolonged ulnar nerve stimulation, suggesting that the changes in MEP areas were not the result of stimulus-induced increases in the excitability of spinal motoneurones. Control experiments employing transcranial electric stimulation provided no evidence for a spinal origin for the excitability changes. These results demonstrate that in normal human subjects the excitability of the cortical projection to hand muscles can be altered in a manner determined by the peripheral stimulus applied.

Assessment of dorsal nerve root and spinal cord dorsal horn function in clinically normal dogs by determination of cord dorsum potentials

Abstract Objective To establish normal predictive values for cord dorsum potential (CDP) onset latency after thoracic and pelvic limb sensory or mixed nerve stimulation in adult dogs. Animals 26 clinically normal adult dogs. Procedure Sensory nerve action potentials (SNAP) were recorded proximally from tibial and lateral superficial radial nerves after distal stimulation. The CDP were recorded from the L4-L5 interarcuate ligament for the tibial nerve and from the C7-T1 interarcuate ligament for the radial nerve. Linear regression analyses were performed for CDP onset latency, and mean ± SD was calculated for CDP onset to peak latency differences and sensory nerve conduction velocities (SNCV). Results For the tibial nerve, expected CDP onset latency (CDPOL) = −1.194 + 0.014 × pelvic limb length (mm; R2 = 0.912); CDPOL = −2.156 + 0.011 × pelvic limb/spinal length (mm; R2 = 0.911); and CDPOL = 0.941 + 2.197 × tibial nerve SNAP latency (milliseconds; R2 = 0.903). For the radial nerve, CDPOL = −0.9 + 0.014 × thoracic limb length (mm; R2 = 0.873); and CDPOL = 1.454 + 1.874 × radial nerve SNAP latency (milliseconds; R2 = 0.903). Mean ± SD for CDP onset to peak latency difference for tibial and radial nerves was 3.1 ± 0.3 and 3.0 ± 0.4 milliseconds, respectively. Conclusions Strong linear associations exist between CDPOL and a number of easily measured peripheral independent variables in dogs. There is also a narrow range of normal values for CDP onset to peak latency differences that is independent of limb length. Clinical Relevance CDP evaluation can be used to accurately assess functional severity and distribution of abnormalities in proximal sensory nerves, dorsal nerve roots, and spinal cord dorsal horns in dogs with suspected neuropathy, radiculopathy, or myelopathy involving the brachial or lumbosacral intumescences. (Am J Vet Res 1999;60:222-226)

Intra-operative spinal cord neuromonitoring in patients operated on for intramedullary tumors and syringomyelia

Intra-operative neuromonitoring is of great help to the neurosurgeon and enables him to operate more precisely and with less risk of post-operative neurological deficit. The purpose of the study was to define the changes of the somatosensory evoked potentials (SEP) elements in intramedullary tumors and syringomyelia, and to show the correlation between the changes of the elements and the location of the lesions in the spinal cord. Thirty patients with pain syndromes, intramedullary tumors and syringomyelia were operated on the spinal cord. The methodology of the intra-operative neuromonitoring was based on electrical stimulation of peripheral mixed nerve (tibial and median), and on intra-operative subpial recording of conducted and interneuronic SEP from the dorsal surface of the spinal cord. The recordings in pain syndrome cases were normal, and were compared with recordings obtained in syringomyelia and tumors. The most stable element of the conducted SEP are the initial negative waves that originate in the spinocerebellar tract. Deterioration of the negative high amplitude potentials is the most sensitive indicator of damage to the somatosensory system of the spinal cord, and indicates damage to the dorsal columns. The N11 and N14 waves are the most stable elements of the cervical and lumbosacral interneuronic SEP, and most probably originate in the dorsal root entry zone. Changes of the NI3 and NI7 elements of interneuronic SEP suggest damage to the spinal cord gray matter, and are most frequently changed in intramedullary lesions. High frequency waves seen on N13 or Ml 7 probably reflect the somatosensory long tracts, and are even better seen in syringomyelia and pure intramedullary tumors. Changes in the elements of interneuronic and conductive SEP enable us to localize the anatomical site of the lesion, which is of great help to the operating neurosurgeon. [Neurol Res 1999; 21: 125–129]

A measure of peripheral nerve stimulation efficacy applicable to H-reflex studies.

When H-reflexes are recorded during movement in human subjects, the stimulator current output is not a good indicator of sensory stimulation efficacy because of unavoidable nerve movement relative to the stimulus electrodes. Therefore, the M-wave amplitude has been used by researchers as an indicator of the efficacy of the stimulus. In this study we have examined the general validity of the hypothesis that the M-wave amplitude is directly proportional to the group I sensory afferent volley evoked by the stimulus. A nerve recording cuff, stimulating electrodes, and EMG recording electrodes were implanted in cats. Nerve cuff recordings of centrally propagating volleys evoked by electrical stimuli were directly compared to M-waves produced by the same stimuli. Compound action potentials (CAPs) recorded in the sciatic nerve were compared with soleus M-waves during either tibial nerve or soleus muscle nerve stimulation. CAPs in the ulnar nerve were correlated with flexor carpi ulnaris M-waves during ulnar nerve stimulation. Our findings indicate that for mixed nerve stimulation (e.g., tibial or ulnar nerve) the M-wave can be a reliable indicator of the centrally propagating sensory volley. Due to the high correlation between CAP and M-wave amplitude in these nerves, a small number of M-waves can give a good estimate of the size of the group I sensory volley. On the other hand, when nerves with only partially overlapping fibre diameter populations are stimulated (e.g., the soleus muscle nerve), the M-wave is not well correlated with the group I sensory volley and thus may not be used as a measure of the size of the input volley for H-reflex studies.

Central nervous system plasticity after spinal cord injury in man: interlimb reflexes and the influence of cutaneous stimulation

In persons who have sustained severe injuries to the cervical spinal cord, electrical stimulation of mixed peripheral nerves in a lower limb can evoke short-latency, bilateral motor responses in muscles of the distal upper limbs; such motor responses have been termed interlimb reflexes. In the present study, we investigated the role that cutaneous stimulation plays in evoking interlimb reflexes. Fifteen subjects with chronic injury (>1 year) to the cervical spinal cord were investigated. Single motor unit activity was recorded from a number of distal upper limb muscles. The lower limb cutaneous area within which stimulation recruited a given motor unit of the upper limb was defined as that motor unit's ‘receptive field’. Activity from a total of 48 single motor units was analyzed. The majority of motor units responded to light touch, individual hair movement, and thermal (hot and cold) stimulation. Excitatory responses were observed bilaterally, although contralateral responses predominated. Stimulation occasionally resulted in inhibition of a spontaneously active motor unit. Receptive fields varied a great deal in size, with proximal locations being larger than those encountered in more distal lower limb locations (i.e. the toes). The spinocervical tract is a possible candidate for mediating some portion of these interlimb reflexes, the origin of which may be due to new growth (regenerative sprouting) in the spinal cord caudal to a severe injury.

Facilitation of magnetic motor evoked potentials during the mixed nerve silent period.

We studied motor neuron excitability during the mixed nerve silent period (MNSP) in a hand muscle using magnetic motor evoked potentials (MEPs) and F-waves. MEPs elicited between the V1 and V2 potentials of the MNSP were much larger than control MEPs elicited at rest, and were even comparable in size to control MEPs elicited during voluntary contraction. This facilitation of MEPs occurred without shortening of MEP latency, suggesting a supraspinal mechanism. MEPs were facilitated during the MNSP when elicited with a figure-8-shaped coil in a posterior-anterior orientation, but not when MEPs of the same size were elicited with the coil held in a lateral-medial orientation. F-waves elicited during the MNSP were variable between subjects, and not consistently different from control F-waves elicited at rest. Our findings may reflect increased cortical motor excitability during the MNSP, possibly related to activation of muscle afferents by mixed nerve stimulation.

Late facilitations of motor evoked potentials by contralateral mixed nerve stimulation

The effect on motor evoked potentials (MEPs) of a peripheral afferent volley (a single square pulse delivered to the contralateral median nerve at the wrist) was studied in abductor digiti minimi muscle of 9 normal patients following magnetic stimulation of the motor cortex. Long intervals were used (200–700 cosec) between the electrical conditioning stimulus and magnetic test stimulation. An MEP amplitude increase, with no change in latency, was observed when the C-T interval was about 500 cosec, and the motor threshold was decreased by the conditioning stimulation. The observed long latency and duration of the facilitation effect would seem consistent with activation of suprasegmental areas.

Conduction abnormalities detected by silent period testing

Cutaneous and mixed nerve silent periods (SPs) were analyzed in 2 patients with pure sensory neuropathy and in 5 healthy controls. In patients, sensory nerve action potentials (SNAPs) and somatosensory evoked potentials (SEPs) were absent, but digital and mixed nerve stimulation evoked complete SPs in voluntarily contracting thenar muscles. Marked differences in SP latencies were found between the patients, despite shared diagnoses and virtually identical nerve conduction studies. When compared with controls, SPs were normal in the first patient and markedly delayed in the second. Such findings suggest that SPs can identify conduction abnormalities not detected by routine studies. The pathologic correlate to these abnormalities remains uncertain, although electrophysiologic data suggest that the smaller, slower conducting delta fibers carry the impulses that generate these SPs.

Dermatomal Somatosensory Evoked Potentials: Methodology and Clinical Applications

Dermatomal somatosensory evoked potentials (DSEPs) have been recently added to the armamentarium of techniques that address segmental level issues of spinal cord and nerve roots. Although DSEPs are technically similar to evoked potential to mixed nerve stimulation, good results depend on attention to factors such as stimulating electrode size and location, recording electrode location, alertness, protocol design, and waveform analysis. DSEPs have been used successfully in single-level and multiple-level root disease and in segmental-level evaluation of spinal cord involvement. Compared to other techniques, DSEPs have been at least as successful in identifying abnormalities, and, in some cases, mo-reso. In fact, for the thoracic levels, DSEPs may be considered a unique noninvasive method.

Sudomotor skin responses to brain stimulation do not depend on nerve sensory fiber functionality

Evaluation of sudomotor innervation to the limbs was performed via electrical stimulation of the median nerve at the wrist and transcranial magnetic stimulation of the brain. Sympathetic skin responses (SSRs) from the palms and the soles were recorded in a patient suffering from a form of predominantly sensory neuropathy. Motor responses to nerve stimulation were present, even if with slower than normal conduction velocity. However, median, ulnar and sural nerve sensory potentials were absent. SSRs to median nerve stimulation at the wrist were missing on palms and soles. By contrast, during brain stimulation of the hand motor area with magnetic impulses, SSRs were reliably identifiable at all recording sites. It is hypothesized that SSRs to mixed nerve stimulation need normal functionality of afferent fibers, while those to brain stimulation can be elicited without any sensory information from the limbs.

Up and Down the Spinal Cord: Intraoperative Monitoring of Sensory and Motor Spinal Cord Pathways

Monitoring of spinal cord function during certain orthopedic and neurosurgical procedures is done to reduce the likelihood of neurologic complications. This article is based on intraoperative experiences gained at Duke University Medical Center since 1978. Both ascending sensory (up) and descending motor (down) data can be evaluated to assist in improved patient outcomes. Refinements in technique and better understanding of the neural generators of evoked potentials obligate the components to have improved sensitivity and specificity of spinal intraoperative monitoring. An additional improvement has been the intraoperative use of motor evoked potentials. This discussion deals with a description of specific responses obtained following lower-limb mixed nerve stimulation in terms of neural generation, influences of rate and intensity, and anesthetic effects. The techniques and advantages of bipolar epidural recording and stimulation are discussed. Motor tract stimulation via the same epidural electrodes used for recording of sensory components is described. Case reports are presented to emphasize major points.

Physiological basis of voluntary activity inhibition induced by transcranial cortical stimulation

Apart from exciting corticospinal cells and evoking a motor response, electrical or magnetic transcranial cortical stimulation (TCCS) delivered during voluntary activity produces a prolonged inhibition of activity, a silent period (SP), that can last up to 280 msec. The SP duration after TCCS is directly proportional to stimulus intensity. To determine the anatomic substrate and underlying physiological properties of the SP from TCCS, we (1) compared the SP from TCCS with the SP from cutaneous and mixed nerve stimulation, (2) studied the excitability cycle of spinal motor neurons in 3 double stimulus conditions: (a) after paired peripheral nerve stimulation, (b) after TCCS and peripheral nerve stimulation, and (c) after paired electrical TCCS, (3) investigated the timing of the excitability of the sensorimotor cortex measuring long latency responses from median nerve stimulation delivered inside the SP from TCCS. We found that after TCCS, spinal motor neuron segmental excitability is reduced for a period up to 100 msec. Inhibition at a suprasegmental, possibly cortical, level was even more prolonged for a period up to 160 msec, suggesting that at least the late part of the SP after TCCS is due to supraspinal inhibition. Determining the nature of the supraspinal inhibition such as the possible role of cortical inhibitory mechanisms may be useful in further understanding central mechanisms of voluntary motor control and sensorimotor processing.

The silent period produced by electrical stimulation of mixed peripheral nerves

The electromyographic silent period (SP) produced by electrical stimulation of the median and ulnar nerve, before and after lidocaine block of the ulnar nerve at the elbow, was recorded in the voluntarily contracting abductor pollicis brevis (APB) muscle of 4 normal subjects. Prior to block, stimulation of the corresponding segment in either nerve (e.g., wrist and elbow) elicited SPs with similar end points. With more proximal stimulation, the SPs consistently ended earlier. Following the block, ulnar nerve stimulation below the elbow failed to elicit a SP in any subject, despite a mechanical twitch caused by the antagonistic contraction of adductor pollicis muscle. Ulnar nerve stimulation above the block elicited a SP in all subjects similar to the preblock SP. In all 4 subjects, submaximal median nerve stimulation at the wrist produced an H-reflex, followed by a SP in the absence of the direct M-response. This SP, due to selective activation of sensory fibers, lacked a collision component, but, was otherwise similar to the SP elicited by supramaximal wrist stimulation. These findings indicate that the ascending volley following electrical stimulation of a mixed peripheral nerve produces the SP without apparent contribution from the descending motor volley.

The effect of stimulus rate upon common peroneal, posterior tibial, and sural nerve somatosensory evoked potentials

We examined the effect of stimulus rate on somatosensory evoked potentials (SEPs) following stimulation of the common peroneal nerve (CPN) at the knee, and the posterior tibial nerve (PTN) and sural nerve (SN) at the ankle. We measured the amplitude of P40-N50 and N50-P60 in the PTN-SEP and corresponding amplitude of CPN-SEP and SN-SEP at the rate of 2.3, 3.4, 4.1, and 5.1 Hz. When the stimulation rate was increased from 2.3 to 5.1 Hz, the P40-N50 amplitude decreased by 50% for the CPN-SEP and 20% for the PTN-SEP. Also, the N50-P60 amplitude was reduced by 30% in the CPN-SEP and 20% in the PTN-SEP. In contrast, this change in stimulus rate produced no significant amplitude decline in the SN-SEP. Blocking the peroneal nerve with lidocaine just distal to the stimulating electrodes eliminated the descending peroneal nerve volley and abolished the amplitude attenuation observed with the faster stimulus rate. The findings suggest that at higher rates of stimulation, the afferent volleys induced by the movements that follow mixed nerve stimulation interfere with the SEP produced by electrical activation of the sensory afferents. The interference is greater when the more proximal site of the mixed nerve is stimulated.

The influence of contralateral primary afferents on Ia inhibitory interneurones in humans.

1. Contralateral influences on short latency reciprocal inhibition between wrist extensor and flexor muscles were investigated in twenty-two healthy volunteers. Reciprocal inhibition, probably mediated through the Ia inhibitory interneurone, was measured by conditioning the flexor carpi radialis (FCR) H reflex by weak stimulation of the ipsilateral radial nerve. Maximum reciprocal inhibition occurring at a precise delay between conditioning and conditioned stimulations was taken as the test level of inhibition. 2. Contralateral median or radial nerves were stimulated at short intervals before the onset of reciprocal inhibition. The latter was increased by 8.6% after median nerve stimulation and decreased by 16.5% after radial nerve stimulation. 3. The contribution of sensory fibres in the two nerves to contralateral effects was investigated by stimulating purely sensory branches of the nerves. No clear modification of the contralateral reciprocal inhibition was observed. The effects produced by mixed nerve stimulation are thus likely to have been mediated by Ia fibres. 4. In three hemiplegic patients where reciprocal inhibition was reduced unilaterally, stimulation on the spastic side produced contralateral effects similar to those observed in normal subjects. This result indicates that contralateral effects are not mediated through the Ia inhibitory interneurone ipsilateral to the conditioning stimulus. 5. Since contralateral effects occur after short delays (2 ms, median nerve; 3 ms, radial nerve), we suggest a functional scheme in which the excitability of Ia inhibitory interneurones is modified by contralateral primary afferents via the interneurones activated by group I fibres, probably Ia fibres. The short delays indicate that the interneurone transmitting primary afferent influences to the contralateral side is probably excitatory.

Pattern of cutaneous inhibition of the propriospinal‐like excitation to human upper limb motoneurones.

1. The pattern of cutaneous inhibition of non-monosynaptic excitation (or 'propriospinal-like' excitation) to various species of motoneurones-wrist flexors and extensors, biceps and deltoid - was investigated in man. 2. Changes in the firing probability of individual voluntarily activated motor units were studied following various stimuli. The effects of weak cutaneous stimuli applied to the skin of either the palmar or the dorsal side of the fingers on propriospinal-like excitation evoked by stimulation of different mixed nerves (median, radial, musculo-cutaneous) were investigated. 3. Cutaneous stimuli were found to produce an inhibition with a very specific pattern, which depended on the afferent input evoking the excitation. Thus, the median nerve-induced excitation of wrist and elbow flexors was depressed by cutaneous afferents from the palmar side but not from the dorsal side of the fingers; the radial nerve-induced excitation of wrist extensors was only depressed from the dorsal side: the musculo-cutaneous nerve-induced excitation of motor units of various wrist, elbow and shoulder muscles was depressed from both sides. 4. It is argued that this pattern implies that the excitation is mediated to the motoneurones through different subsets of neurones, organized according to the afferent input. 5. The functional significance of the pattern of cutaneous inhibition is discussed and it is argued that it could contribute to an appropriately timed termination of a movement mediated through the propriospinal system.

Influences of transcutaneous electrical stimulation of cutaneous and mixed nerves on subcortical and cortical somatosensory evoked potentials

Aim of this study was to assess whether transcutaneous electrical nerve stimulation (TENS) ‘gates’ somatosensory evoked potentials (EPs) peripherally or centrally, and which afferent fibres and sensory nuclei mediate this effect. The following waves were recorded after stimulation of the median nerve at the wrist or of the digital nerves of the index finger: N9, the cervical N11 and N13, the parietal P9, P11, P14, N18, N20, P22, P27, P40. When both median or digital nerve EPs were conditioned by TENS delivered to the median nerve, reduction in amplitude of N9, P14, N18 and later generated cortical waves was observed. To measure the central contribution to this decrease, unconditioned ‘reference’ EPs were evoked by stimulating with a current strength yielding an N9 potential of an amplitude equal to that obtained during TENS. In this case, the amplitude of P14, N18 and later cortical waves was significantly greater than during TENS. When both median or digital nerve EPs were conditioned by TENS delivered to the digital nerves, waves were only slightly affected. No effects were seen on the EPs elicited from the median or index finger digital nerves when TENS was administered to the contralateral median or digital nerves or to the ipsilateral middle finger. It is concluded that TENS gates the somatosensory volley, both at a peripheral level through a ‘busy line-effect’ on large afferent fibres, and centrally at the level of the cuneatus nucleus.

Galanin release during pancreatic nerve stimulation is sufficient to influence islet function

To determine if galanin is released during pancreatic neural activation, we measured galanin-like immunoreactivity (GLIR) in pancreatic venous and peripheral arterial plasma during 10 min of electrical stimulation of the mixed autonomic pancreatic nerves in halothane-anesthetized dogs, using a sensitive and specific radioimmunoassay. During mixed pancreatic nerve stimulation (MPNS), pancreatic venous GLIR increased by 174 +/- 20 fmol/ml, whereas arterial GLIR did not change. By use of the arteriovenous concentration difference and measurements of pancreatic venous blood flow, pancreatic spillover of GLIR was calculated and found to increase by 640 +/- 90 fmol/min during MPNS. This MPNS inhibited the output of immunoreactive insulin (IRI; delta = -53 +/- 9%) and somatostatin-like immunoreactivity (SLI, delta = -49 +/- 13%) and stimulated that of immunoreactive glucagon (IRG, delta = +600 +/- 200%). To determine if the amount of GLIR released during MPNS was sufficient to elicit these changes of pancreatic hormone secretion, we compared the effect of MPNS on IRI, SLI, and IRG output with the effect of synthetic galanin infused directly into the pancreatic artery at a rate that reproduced the MPNS-induced spillover of GLIR. Exogenous infusion of synthetic galanin (2.7 pmol/min) increased pancreatic venous levels of GLIR by 169 +/- 38 fmol/ml, did not change arterial GLIR levels, and thus increased calculated spillover (appearance) by 550 +/- 160 fmol/min, which was nearly identical to the increment produced by MPNS. This matched infusion of galanin inhibited IRI (delta = -58 +/- 3%) and SLI output (delta = -35 +/- 3%) and modestly stimulated IRG output (delta = +62 +/- 10%).(ABSTRACT TRUNCATED AT 250 WORDS)