Trigeminocervical reflexes elicited by stimulation of the infraorbital nerve: head retraction reflex.

In the current study, the effects of stimulation of the infraorbital nerve (ION) on the trigeminocervical reflexes (TCRs), recorded from the posterior neck muscles, was investigated and the results were compared with the results recorded by stimulation of the supraorbital nerve (SON). TCRs obtained by stimulation of the ION was evaluated as the electrophysiologic counterpart of the head retraction reflex. Twenty normal control subjects, 10 men and 10 women, were enrolled in the study. The SON and the ION were stimulated by using a bipolar surface electrode. Results were recorded by using either concentric needle electrodes inserted into the semispinalis capitis muscle at the level of the third or fourth cervical vertebra or by surface electrodes placed at the C3 and C7 vertebrae on the midline. It was found that stimulation of the supraorbital and infraorbital branches of the trigeminal nerve had different reflexive effects on the posterior neck muscles. A stable positive (or negative-positive) wave, with a very early latency and high amplitude was always recorded after maximal stimulation of the ION, which could never be detected by stimulation of the SON. The C3 response of the TCR, evoked by SON stimulation was always evoked, by stimulation of the ION, at a low threshold. These findings suggest that the head retraction reflex is composed of two phases: inhibitory and excitatory. The early, fixed positive wave represents the general inhibition of the cranial and neck muscles, just before withdrawal of the face and head, from unexpected stimuli, which precedes the dense C3 response, demonstrating activation of the posterior neck muscles.     

Prepulse inhibition and recovery of trigemino-cervical reflex in patients with cervical dystonia

ObjectiveWe aimed to analyze the prepulse inhibition (PPI) and recovery rate (R) of the trigeminocervical reflex (TCR) in patients with cervical dystonia (CD).MethodsWe enrolled 15 patients with CD and 16 healthy subjects. TCR was recorded over splenius capitis after infraorbital nerve stimulation. For TCR-PPI, we applied a prepulse stimulus to the left second finger 100 ms prior to the test stimulus and the percentage of change of response to test stimulus was calculated. For TCR-R, we applied paired infraorbital stimuli at interstimulus interval (ISIs) of 300 ms and the percentage of change of the second compared to the first response was calculated.ResultsTCR-PPI and TCR-R values were higher (less inhibition and greater recovery) on both sides in the patient group compared to healthy subjects. There was high correlation between TCR-PPI and TCR-R on both sides in patients with dystonia (p < 0.005). We did not find any significant relationship between TCR-R or TCR-PPI and side of dystonic posture.ConclusionsWe showed disturbed modulation of TCR in CD patients. In CD, a general inhibition of the inhibitory pathways and facilitation of the excitatory pathways occur. Although TCR was recorded directly on the affected muscles in CD, symmetric abnormal TCR findings in CD suggest that these findings are probably secondary to altered function of higher order centers rather than being directly related to the pathophysiological process.     

Experimental study of a late response recorded from the thoracic wall after phrenic nerve stimulation

ObjectivesThe phrenic nerve cervical stimulation induces an early motor diaphragmatic M response that may be recorded from the 7th ipsilateral intercostal space (ICS). Some responses with prolonged latency and of unclear origin can be recorded from the same recording site. The aim of the study was to determine the electrophysiological characteristics and the neuroanatomical pathways underlying the long-latency responses (LLRs) recorded from the 7th ICS.MethodsWe studied seven healthy volunteers, five patients with spinal cord injury and five patients with diaphragmatic palsy. All underwent phrenic nerve conduction study. An LLR was sought for at different stimulation sites using various stimulus intensities.ResultsA polyphasic LLR was recorded from the 7th ICS in all healthy subjects. It was mainly elicited by nociceptive stimulations, not only of the phrenic, but also of the median nerves. Its latency was longer than 70 ms, with a wide inter- and intra-individual variability. Amplitude was highly variable and some habituation phenomenon occurred. The LLR was retained in most tetraplegic patients after phrenic nerve stimulation, but absent otherwise. It was present in all patients with diaphragmatic palsy after phrenic nerve stimulation.ConclusionThe LLR is likely to be produced by both intercostal and diaphragm muscles. It is a polysynaptic and multisegmental spinal response, probably conveyed by small-diameter nociceptive A-δ and/or C fibres and modulated by a supraspinal control.SignificanceThe LLR recorded from the chest wall may constitute, by analogy with the nociceptive component of the lower limb flexion reflex in humans, a protective and withdrawal spinal reflex response.     

A new method to increase nociception specificity of the human blink reflex.

OBJECTIVE: The medullary R2 response of the blink reflex can be elicited by innocuous and noxious stimuli. The purpose of this study was to elicit a nociception specific R2 response with a new surface electrode. METHODS: In 10 healthy subjects the blink reflex was elicited using a standard (10-15 mA) and a new concentric surface electrode type (0.6-1.6 mA) which produces a pin-prick-like pain. RESULTS: After topical local anaesthesia with lignocaine/prilocaine R1 was unchanged, R2 was attenuated by 12% after standard stimulation but was almost abolished (-91%) with the new electrode type. CONCLUSION: Stimulation with low stimulus intensities but electrode-dependent high current density allows preferential depolarization of superficial nociceptive A-delta fibres. This new method is less traumatic than others and is useful in the study of trigeminal nociception.     

Habituation of the nociceptive flexion reflex is dependent on inter-stimulus interval and stimulus intensity

The nociceptive flexion reflex (NFR) has become a popular tool in experimental and clinical pain research. However, the gradual decrease of the reflex size during repeated application of stimuli, which is termed habituation, may reduce its validity and the comparability of studies. We investigated the degree of habituation at different inter-stimulus intervals (ISI) commonly used in clinical studies and the dependency of habituation on stimulus intensity. Thirty subjects each received 12 sets of 50 stimuli to elicit the NFR at ISI of 1, 3, 6 and 10 s, each at stimulus intensities of 1×, 1.5× and 2× the individual NFR-threshold. For each of the sets, the habituation was calculated as the relative size of the average of the last 10 reflexes compared to the average of the first 10 reflexes. The influence of the factors ISI and stimulus intensity, as well as the factor interaction, was tested using a two-way analysis of variance (ANOVA). Analysis proved that influences of ISI and stimulus intensity on reflex habituation were significant (p < 0.01, two-way ANOVA), while the interaction between the two factors had no significant influence (p = 0.99). We conclude that habituation of the NFR is dependent on ISI and stimulus intensity. Lower stimulus intensities and shorter ISI lead to stronger habituation. Therefore, to ensure habituation is avoided during repeated elicitation of the NFR, stimulation should be conducted according to the ISI for the respective stimulus intensities presented here.     

Sympathetic skin responses: the influence of electrical stimulus intensity and habituation on the waveform

Abstract Repeated stimulation of the sympathetic skin response (SSR) causes habituation. The aim of this study was to determine the effects of electrical stimulus intensity on SSR in 40 healthy controls (mean age±SD, 28.0±6.7 years). Electrical stimuli at three intensities (5, 15 and 30 mA) were applied to the median nerve at the wrist in four consecutive sessions, after which a magnetic stimulus was applied to the neck. SSR were classified according to the proportion of positive (P) and negative (N) waveform components.Twentyfour subjects had both P and N waveforms. In the first session, 75% of these subjects had a P waveform, indicative of a greater SSR, in response to the 30 mA shock. In the progressive sessions, the SSR waveform was predominately negative (N waveform, session 2, 65%; session 3, 83%; session 4, 75% in response to 30 mA shock), indicating that the SSR was weaker as a result of habituation. There was no clear relationship between stimulus intensity and waveform type, indicating that SSR waveforms are more strongly influenced by habituation than stimulus intensity. However, there was a directly proportional relationship between stimulus intensity and amplitude of the SSR wave (F=70.9, P<0.0001, two-way repeated measure ANOVA), be it positive or negative. The relationship between stimulus intensity and amplitude persisted, even after habituation. Suddenly switching to a magnetic stimulus reverted the SSR wave back to positive (80%), indicating that habituation was rapidly reversible if stimulation of the SSR is altered.     

Habituation of the blink reflex: computer assisted quantitative analysis

The electrically evoked blink reflex (BR) was elicited in 20 healthy volunteers, varying the stimulus interval by a computer JN 110. Latencies, amplitudes, reflex duration and reflex areas of early and late components of the BR were analysed by a computer program testing the signal-to-noise ratio, the response configuration and frequency distribution. Changes in habituation related to the stimulus interval can be illustrated best by the progressive diminution of R2 areas. Computing the habituation in relation to the stimulation frequency by a standardized program seems to be a quantitative method to assess habituation in various diseases and during treatment studies.     

Trigemino-cervical-spinal reflexes in humans.

INTRODUCTION: Electrical stimulation of the supraorbital nerve (SON) induces late reflex responses in the neck muscles; these responses are hypothesised to be polysynaptic reflexes participating in a defensive withdrawal retraction of the head from facial nociceptive stimuli. Such responses may extend to the proximal muscle of the arms. OBJECTIVE: (1) to investigate reflexes in the upper limb muscles (trigemino-spinal responses, TSR) and their relationship with trigemino-cervical responses (TCR); and (2) to identify the nociceptive component of such reflexes and their functional significance. METHODS: Reflex responses were registered from the semispinalis capitis and biceps brachii muscles after electrical stimulation of the SON in 12 healthy subjects. The sensory (ST), painful (PT) and reflex thresholds, the latency and area of the responses, the effect of heterotopic painful stimulation (HTP), the recovery cycle as well as the effect of the expected and unexpected stimuli were measured. RESULTS: Stable reproducible TCR and TSR responses were identified at 2.5+/-0.4 x ST, which corresponded exactly to the PT in all the subjects. The TCR and TSR areas were markedly reduced after HTP. The recovery cycle of the TSR area was faster than that of the TCR. Repeated rhythmic stimulation failed to induce progressive reflex suppression. CONCLUSIONS: These results confirm the nociceptive nature of the TCR and indicate that the biceps brachii response (TSR) has the same nocifensive significance as the posterior neck muscle responses. TCR and TSR are mediated different polysynaptic pathways The presence of trigemino-cervical-spinal responses in our study clearly indicates that there is a reflex interaction between nociceptive trigeminal afferents and both upper and lower cervical spinal cord motoneurons.     

Comparative study of the nociceptive reflex and late components of the evoked somatosensory potential during stimulation of the sural nerve in healthy subjects

A study was carried out with 10 normal volunteers in order to find a correlation between nociceptive flexion reflexes from the biceps femoris muscle and the amplitude of the late component (N150-P220) of the vertex evoked potential elicited by sural nerve stimulations at various intensities randomly delivered. The range of stimulus varied from the perception threshold (usually 1 mA) to 2 times the reflex threshold. This latter parameter was usually found between 8 and 11 mA. While the nociceptive flexion reflex increased linearly as a function of stimulation intensity, the amplitude of N150-P220 was maximum at pain threshold and remained in plateau at this level or even slightly decreased as a function of stimulus intensity. No significant correlation was found between the recruitment curve of the nociceptive reflex and that of the late component of the evoked potential as a function of stimulus intensity. Functional implications of these data are discussed.     

Magnetic and electric stimulation to elicit the masseteric exteroceptive suppression period

ObjectivesThe present study compared the perception of electric and magnetic stimuli for reflex appearance threshold (RT) and reflex saturation threshold (RS) of the exteroceptive suppression reflex (ES) in the masseter muscle.MethodsTwelve healthy males and 12 females (age: 24.2 ± 3.2 years) participated. The surface EMG was recorded from the left masseter muscle. The stimulus intensities were set as multiple values of the sensory threshold (ST), and were applied to the skin above the left mental nerve. Subjects reported the perceived intensity of the stimulus on a numeric rating scale (NRS) at RT and RS for the early and late ES (ES1 and ES2, respectively).ResultsES2 had a lower RT and RS compared to ES1 in electric and magnetic stimulation. Significantly lower NRS values at RT and RS were found with painless magnetic stimulation compared to electric stimulation (p < 0.01).ConclusionsIn contrast to electrical stimulation, both ES1 and ES2 appeared and saturated with painless magnetic stimuli.SignificanceThe present results indicate that both ES1 and ES2 have a non-nociceptive origin. Painless magnetic stimuli will be an advantage in ES reflex examinations for various orofacial pain conditions.     

Electrical low-frequency stimulation induces homotopic long-term depression of nociception and pain from hand in man

OBJECTIVE: Electrical low-frequency stimulation (LFS) of cutaneous afferents evokes long-term depression (LTD) of nociception. In vitro studies suggest a sole homosynaptic effect on the conditioned pathway. The present study addresses homotopy of LTD in human nociception and pain. METHODS: In 30 healthy volunteers, nociceptive Adelta fibers were electrically stimulated by a concentric electrode. Test stimulation (0.125 Hz) was alternately applied unilateral to radial and ulnar side of right hand dorsum (ExpUni) or bilateral to radial side of right and left hand dorsum (ExpBi). Conditioning LFS (1 Hz, 1,200 pulses) was applied to radial side of right hand dorsum. Somatosensory evoked cortical vertex potentials (SEP) were recorded, and volunteers rated stimulus intensity. RESULTS: After homotopic LFS, SEP amplitude (ExpUni: -34.6%; ExpBi: -33.6%) and pain rating (ExpUni: -44.1%; ExpBi: -29.1%) significantly decreased. Amplitude reduction after heterotopic LFS did not differ from habituation effects in Control experiment without LFS. Heterotopic pain perception was not affected. CONCLUSIONS: The electrophysiological and psychophysical study on synaptic plasticity in healthy man demonstrates homotopic organization of LTD. SIGNIFICANCE: Homotopy is probably due to a homosynaptic effect at first nociceptive synapse, but descending inhibitory systems may also be involved. These experiments may help to judge the potency of LTD for future therapy in chronic pain.     

Small nerve fiber selectivity of laser and intraepidermal electrical stimulation: A comparative study between glabrous and hairy skin

ObjectivesIn clinical neurophysiology practice, various methods of stimulation can be used to activate small-diameter nociceptive cutaneous afferents located in the epidermis. These methods include different types of laser and intraepidermal electrical stimulation techniques. The diffusion of the stimulation in the skin, inside or under the epidermis, depends on laser wavelength and electrode design, in particular. The aim of this study was to compare several of these techniques in their ability to selectively stimulate small nerve fibers.MethodsIn 8 healthy subjects, laser stimulation (using a CO₂ or Nd:YAP laser) and intraepidermal electrical stimulation (using a micropatterned, concentric planar, or concentric needle electrode), were applied at increasing energy or intensity on the dorsal or volar aspect of the right hand or foot. The subjects were asked to define the perceived sensation (warm, pinprick, or electric shock sensation, corresponding to the activation of C fibers, Aδ fibers, or Aβ fibers, respectively) after each stimulation. Depending on the difference in the sensations perceived between dorsal (hairy skin with thin stratum corneum) and volar (glabrous skin with thick stratum corneum) stimulations, the diffusion of the stimulation inside or under the epidermis and the nature of the activated afferents were determined.ResultsRegarding laser stimulation, the perceived sensations turned from warm to pinprick with increasing energies of stimulation, in particular with the Nd:YAP laser, of which pulse could penetrate deep in the skin according to its short wavelength. In contrast, CO₂ laser stimulation produced only warm sensations and no pricking sensation when applied to the glabrous skin, perhaps due to a thicker stratum corneum and the shallow penetration of the CO₂ laser pulse. Regarding intraepidermal electrical stimulation using concentric electrodes, the perceived sensations turned from pinprick to a combination of pinprick and electrical shocks with increasing intensities. Using the concentric planar electrode, the sensations perceived at high stimulation intensity even consisted of electric shocks without concomitant pinprick. In contrast, using the micropatterned electrode, only pinprick sensations were produced by the stimulation of the hairy skin, while the stimulation of the glabrous skin produced no sensation at all within the limits of stimulation intensities used in this study.ConclusionsUsing the CO₂ laser or the micropatterned electrode, pinprick sensations were selectively produced by the stimulation of hairy skin, while only warm sensation or no sensation at all were produced by the stimulation of glabrous skin. These two techniques appear to be more selective with a limited diffusion of the stimulation into the skin, restricting the activation of sensory afferents to the most superficial and smallest intraepidermal nerve fibers.     

Blink reflexes in chronic tension-type headache patients and healthy controls

ObjectiveTo use the R2 component of nociceptive-specific blink reflex (nBR) to probe the trigeminal nociceptive system and compare chronic tension-type headache (CTTH) patients and healthy controls.MethodsThirty patients with CTTH and 30 age- and sex-matched healthy control subjects were included. nBR were evoked by painful electrical pulses (0.5 ms duration), delivered by a concentric electrode placed on the left lower forehead close to the supraorbital foramen. The EMG activity in the orbicularis oculi muscles was recorded bilaterally. The electrical stimulus intensities to evoke individual sensory threshold (Is) and pin-prick pain sensation (Ip) were assessed. A fixed stimulation intensity of 1.5× Ip was used to evoke the nBR. The perceived pain intensity of the electrical stimulus (I_BR) was assessed by the subjects on a 0–10 cm visual analogue scale (VAS).ResultsIs did not differ between CTTH patients and controls (P = 0.687) but were lower in females than in males (P = 0.020). CTTH patients had higher scores on I_BR than controls (P = 0.026). ANOVA showed significantly higher pre-stimulus EMG values in CTTH patients on the left (stimulated) side (P < 0.001), whereas there were no differences between males and females (P > 0.168). There were no significant differences in the absolute values of the nBR, however CTTH patients had significantly lower values of the normalized root mean square (RMS) (P = 0.035) and area under the curve (AUC) (P = 0.042) of the nBR on the left side compared with control subjects with no sex-related differences (P > 0.070). The onset latencies and duration were not significantly different between CTTH and control subjects or between female and male subjects (P > 0.270). There was no significant correlation between any of the BR parameters (RMS, AUC) and clinical characteristics of CTTH (headache intensity and duration) (P > 0.163).ConclusionsThe results of the present study did not detect a significantly different blink reflex response in CTTH patients, but suggested that painful electrical stimulation was associated with consistent increases in eye muscle activity on the same side.SignificanceThese findings add further information to central nociceptive pathways in CTTH patients.     

Early nociceptive evoked potentials (NEPs) recorded from the scalp

ObjectiveNeurophysiological investigation of nociceptive pathway has so far been limited to late cortical responses. We sought to detect early components of the cortical evoked potentials possibly reflecting primary sensory activity.MethodsThe 150 IDE micropatterned electrode was used to selectively activate Aδ intraepidermic fibres of the right hand dorsum in 25 healthy subjects and 3 patients suffering from trigeminal neuralgia. Neurographic recordings were performed to assess type of stimulated fibres and check selectivity. Cortical evoked potentials were recorded from C3′-Fz and Cz-Au1.ResultsNeurographic recordings confirmed selective activation of Aδ fibres. Early components were detected after repetitive stimulation (0.83/s rate and 250–500 averages); the first negative component occured at 40 ms (N40) on the contralateral scalp.ConclusionsThe provided data support the hypothesis that N40 could be the cortical primary response conducted by fast Aδ fibres.SignificanceThis is the first report of early, possibly primary, cortical responses in humans by nociceptive peripheral stimulation. Although not perfected yet to allow widespread diagnostic use, this is probably the only method to allow fully objective evaluation of the nociceptive system, with important future implications in experimental and clinical neurophysiology.     

SI nociceptive neurons participate in the encoding process by which monkeys perceive the intensity of noxious thermal stimulation

The activity of primary somatosensory (SI) cortical nociceptive neurons was recorded while the monkeys performed a psychophysical task in which they detected small increases in skin temperature superimposed on noxious levels of thermal stimulation. The detection latency to these stimuli, expressed as detection speed, was used as a measure of the perceived intensity of sensation. Two-thirds of the neurons that responded to noxious thermal stimulation increased their discharge in response to graded increases in stimulus intensity. The remaining neurons responded to noxious thermal stimulation, but did not grade their response with the intensity of the stimulus. The response of SI nociceptive neurons that encode the intensity of noxious thermal stimulation was significantly correlated with the monkey's detection speed. We conclude that SI nociceptive neurons are involved in the encoding process by which monkeys perceive the intensity of noxious thermal stimulation.     

Habituation of cutaneomuscular reflexes recorded from the first dorsal interosseous and triceps muscle in man

Cutaneomuscular reflexes have been recorded from the first dorsal interosseous muscle during a sustained abduction of the index finger of 20 subjects (25 recordings) following stimulation of the digital nerves at the following frequencies: 2 Hz, 3 Hz, 5 Hz, 7 Hz and 9 Hz, presented in random order. Five hundred stimuli were given at each frequency. EMG was rectified and consecutive batches of 100 sweeps of each set of 500 responses were averaged time locked to the stimulus. All reflex components, E1, I1 and E2, exhibit habituation with the E1 component habituating the most and the I1 component the least. There was considerable variation in the rate of habituation between subjects. The rate of habituation was independent of the frequency of stimulation. Reflex responses were recorded from the triceps brachii muscle in eight subjects; this reflex response habituated at a faster rate than the E2 component recorded from the first dorsal interosseous muscle. These results are discussed in relation to the choice of stimulus parameters for the clinical testing of cutaneous reflexes. We conclude that it is important to consistently average the same number of responses.     

The palmo-mental reflex. An electrophysiological study.

Repeated electric stimulation of the ulnar nerve fibers was applied at the wrist in 7 normal and 32 pathological subjects; the response reflexes were simultaneously recorded in the chin muscles and at the upper limb, on the flexor carpi ulnaris. Although it is possible to obtain two distinct polysynaptic reflexes by cutaneous stimulation of the limb, the palmo-mental reflex causes a unique response, the latency of which may diminish to 35 msec. This response occurs most often at the threshold which elicits a nociceptive reflex of the upper limb. The palmo-mental reflex is almost always bilateral for a unilateral stimulation and in numerous instances is characterized by a wide receptive field. These findings suggest that the palmo-mental reflex is an early event in a general nociceptive response. In the normal subject this fragment of a general response to a painful stimulus is highly suppressed as are the local reflexes by suprasegmental control. The palmo-mental reflex is liberated and augmented in the event of habitually bilateral lesions of the pyramidal tract or the extra-pyramidal formations.     

The Hoffmann reflex of human plantar foot muscles

Electrical stimulation of the tibial nerve in the popliteal fossa evoked an M wave (10.9 ms) and a late reflex response (38.1 ms) in the plantar foot muscles of all 10 volunteers. The late response had a somewhat lower electrical threshold than the corresponding M wave (8.5 versus 9 mA), and reached a maximum of amplitude when the stimulus intensity was increased, but was strongly suppressed by further increased intensity. A more distal stimulation of the tibial nerve at the ankle shortened the onset latency of the M wave and lengthened that of the late response. The reflex was facilitated by activation of synergists and inhibited by activation of antagonists. We showed that the late response was contaminated neither by volume conducted activity from the soleus muscle, as shown by intramuscular recordings from the abductor hallucis muscle, nor by a F wave, as shown by double stimulation. In summary, we conclude that this late response in human plantar foot muscles corresponded to an H reflex, which may be used to assess alterations of distal motoneuronal excitability. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:732–738, 1998.     

Dissociation between pain and the nociceptive blink reflex during psychological arousal.

OBJECTIVE: To investigate the effect of psychological arousal on pain ratings and the R2 component of the electrically evoked blink reflex to a 'pure' noiciceptive stimulus. METHODS: Pain ratings and R2 to a noiciceptive stimulus (pulse width 0.3ms, 2mA, delivered from a concentric electrode attached to the supraorbital region of the forehead) were investigated in 16 healthy participants before and during a serial subtraction task, and in 16 control participants who sat quietly during nociceptive stimulation. RESULTS: Pain ratings decreased whereas R2 amplitude increased during the serial subtraction task. CONCLUSIONS: Supra-spinal rather than spinal mechanisms inhibited pain perception during psychological arousal. Moreover, psychological arousal facilitated the R2 component of the blink reflex to a nociception-specific stimulus. SIGNIFICANCE: Supra-spinal influences need to be considered during clinical evaluation of the trigeminal nociceptive blink reflex.