Pain-evoked blink reflex

The electrically evoked blink reflex (BR) consists of an ipsilateral R1 component (R1) at 11 ms and two bilateral components R2 at 33 ms and R3 at 83 ms. It is still unclear whether the R2 is mediated by activation of tactile or nociceptive afferents. For testing the nociceptive hypothesis, nociceptors of the supraorbital nerve were selectively activated by infrared laser stimuli in 10 subjects. Only painful laser stimuli evoked a bilateral early polyphasic BR response (LR2) at 71 ms. Stimulation of infraorbital and mental nerve dermatomes was equally effective. A late bilateral reflex response at 130 ms was occasionally observed. Regarding the nociceptor activation time of about 40 ms, onset latencies were within the range of the electrically evoked R2 and R3, respectively. The good accordance of R2 and LR2 may be due to activation of identical nociceptive fibers or to convergence of electrically evoked tactile and laser-elicited nociceptive input onto common multireceptive neurons. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 265–270, 1997.     

Methodological considerations on the use of the blink reflex R3 component in the assessment of pain in man

We define the principal physiological properties of the nociceptive component R3 of the blink reflex (b.r.) on electrical stimulation of the supraorbital nerve, with the aim of supplying some rules for its use in the analysis of pain in man. We explore the relationship between the threshold (th) of R3 and that of pain on stimulation of the trigeminal nerve and the extent to which R3 is modulated by habituation and attentional levels. Both pain th and R3 th correlate significantly with age. The R3 th was always higher than the R2 th. Habituation definitely decreases the amplitude of R3, which easily disappears. Focusing of attention on the stimulus sharply inhibits R3 while distraction increases it. Our findings emphasize the need to take all these aspects into account when designing protocols for the study of pain mechanisms based on the R3 reflex component. This work was partly supported by a grant from the Italian Ministry for the Universities and for Scientific and Technological Research     

Further evidence for a central reorganisation of synaptic connectivity in patients with hypoglossal-facial anastomosis in man

In normal subjects, electrical stimulation of trigeminal mucosal afferents (lingual nerve - V3) can elicit a short latency (12.5+/-0. 3 ms; mean+/-S.D.) reflex response in the ipsilateral genioglossus muscle (Maisonobe et al., Reflexes elicited from cutaneous and mucosal trigeminal afferents in normal human subjects. Brain Res. 1998;810:220-228). In the present study on patients with hypoglossal-facial (XII-VII) nerve anastomoses, we were able to record similar R1-type blink reflex responses in the orbicularis oculi muscles, following stimulation of either supraorbital nerve (V1) or lingual nerve (V3) afferents. However, these responses were not present in normal control subjects. Voluntary swallowing movements produced clear-cut facilitations of the R1 blink reflex response elicited by stimulation of V1 afferents. In a conditioning-test procedure with a variable inter-stimulus interval, the R1 blink reflex response elicited by supraorbital nerve stimulation was facilitated by an ipsilateral mucosal conditioning stimulus in the V3 region. This facilitatory effect was maximal when the two stimuli (conditioning and test) were applied simultaneously. This effect was not observed on the R1 component of the blink reflex in the normal control subjects. These data strongly suggest that in patients with XII-VII anastomoses, but not in normal subjects, both cutaneous (V1) and mucosal (V3) trigeminal afferents project onto the same interneurones in the trigeminal principal sensory nucleus. This clearly supports the idea that peripheral manipulation of the VIIth and the XIIth nerves induces a plastic change within this nucleus.     

Nociceptive R3 reflex in relapsing-remitting multiple sclerosis patients.

Pain in multiple sclerosis (MS) patients has only recently been recognised as a genuine symptom of this disease. It is important to determine whether this pain is the consequence of another symptom of MS or whether it is due to a demyelinating lesion affecting pain pathways. A close relationship has been found between the R3 component of the blink reflex and the pain threshold. The aim of this work was to carry out an objective evaluation of the nociceptive system in MS patients by means of the R3 component of the blink reflex. The study was performed on 20 healthy volunteers and on 20 clinically defined relapsing-remitting MS patients with EDSS not > 3.5, normal R1 and R2 components of the blink-reflex, personal and family anamnesis negative for migraine and trigeminal neuralgia; the patients were not taking drugs at the time of the test. A significant difference was found, between healthy volunteers and patients, for R3 threshold, pain threshold and R3 latency.     

The corneal reflex and the R2 component of the blink reflex

A reflex contraction of the human orbicularis oculi muscles can be evoked by stimulation of either the supraorbital region ("blink reflex") or the cornea ("corneal reflex"). We found that the latency of the corneal reflex was longer, and the duration was longer than the R2 component of the blink reflex. The absolute refractory period of the R2 component of the blink reflex was longer after supraorbital than after corneal conditioning stimulation. When the R2 component of the blink reflex was habituated by repetitive stimuli, stimulation of the cornea still evoked a reflex, but supraorbital stimulation produced only a depressed R2 response. These findings suggest that the two reflexes do not have identical neural connections.     

Reflexes elicited from cutaneous and mucosal trigeminal afferents in normal human subjects

It has been shown that in patients in whom the central stump of the hypoglossal nerve has been anastomosed to the peripheral stump of a lesioned facial nerve, supraorbital nerve stimulation can elicit a short-latency reflex (12.5±0.6 ms; mean±S.D.) in facial muscles similar to the R1 disynaptic blink reflex response, but not followed by an R2 blink reflex component⁴⁶. Thus in addition to replacing the facial neurons at peripheral synapses, these hypoglossal nerves contribute to a trigemino-hypoglossal reflex. The aim of this work was to study the type of reflex activities which can be elicited in both facial and tongue muscles by electrical stimulation of cutaneous (supraorbital nerve) or mucosal (lingual nerve) trigeminal (V) afferents in normal subjects. The results show that although stimulation of cutaneous V1 afferents elicits the well-known double component (R1–R2) blink reflex response in the orbicularis oculi muscles, it does not produce any detectable reflex response in the genioglossus muscle, even during experimental paradigms designed to facilitate the reflex activity. Conversely, stimulation of mucosal V3 afferents can elicit a single reflex response of the R1 type in the genioglossus muscle but not in the orbicularis oculi muscles, even during experimental paradigms designed to facilitate the reflex activity. These data are discussed in terms of two similar but separate circuits for the R1 responses of cutaneous (blink reflex) and mucosal (tongue reflex) origins. They suggest that in patients with hypoglossal-facial (XII–VII) nerve anastomosis, the short-latency trigemino-‘hypoglossal-facial' reflex of the R1 blink reflex type observed in facial muscles following supraorbital nerve stimulation could be due to changes in synaptic effectiveness of the central connectivity within the principal trigeminal nucleus where both cutaneous and mucosal trigeminal afferents project.     

Corneal reflex in normal and pathological subjects

The orbicularis oculi response can be evoked both by mechanical stimulation of the cornea (corneal reflex) and by electrical stimulation of the skin overlying the supraorbital nerve (blink reflex). Mechanical stimuli to the cornea activate A delta and C free nerve endings of the corneal mucosa. Electrical stimuli to the supraorbital nerve activate A beta, A delta and C fibers of the nerve trunk. Both reflexes present a bilateral late response, but the blink reflex shows in addition an early ipsilateral component (R1), which has never been observed with the corneal stimulation in man. We have developed a simple technique of electrical stimulation of the cornea which provides stable responses and allows precise measurements of threshold and latency of the reflex. In normal subjects, the threshold ranged from 50 to 350 microA, and the maximal stimulus that the subject could bear (tolerance level) ranged from 1000 to 2500 microA. The minimal latency to tolerance level stimuli was 39 +/- 3 msec. The latency difference between the direct responses evoked from the two opposite corneas never exceeded 8 msec and the difference between the direct and consensual responses elicited from the same cornea never exceeded 5 msec. An early ipsilateral component similar to the R1 response of the blink reflex was not observed, even with supramaximal stimulation. The electrically evoked corneal reflex was normal in 10 cases of essential trigeminal neuralgia, while the responses showed significant abnormalities in 18 subjects submitted to thermocoagulation of the Gasserian ganglion as a treatment of neuralgic pain, as well as in 2 cases of symptomatic neuralgia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gating of trigemino-facial reflex from low-threshold trigeminal and extratrigeminal cutaneous fibres in humans.

Changes in the size of the test components (R1 and R2) of the trigemino-facial reflex were studied after electrical subliminal conditioning stimulation were applied to the trigeminal, median and sural nerves. After conditioning activation of the trigeminal nerve (below the reflex threshold), the early R1 reflex component showed phasic facilitation, peaking at about 50 ms of interstimulus delay, followed by a long-lasting inhibition recovering at 300-400 ms. The same conditioning stimulation resulted in a monotonic inhibition of the late R2, starting at 15-20 ms, with a maximum at 100-150 ms and lasting 300-400 ms. Intensity threshold for both the R1 and R2 changes ranged from 0.90 to 0.95 times the perception threshold. A similar longlasting inhibition of the R2 reflex response was also seen after conditioning stimulation applied to low-threshold cutaneous afferents of the median and sural nerves. The minimum effective conditioning-test interval was 25-30 ms and 40-45 ms respectively and lasted 600-700 ms. By contrast the early R1 reflex response exhibited a slight long-lasting facilitation with a time course similar to that of the R2 inhibition. The threshold intensity to obtain facilitation of the R1 and inhibition of the R2 test responses after conditioning volley in the median and sural nerves was similar and ranged from 0.9 to 1.2 times the perception threshold. These results demonstrate that low-threshold cutaneous afferents from trigeminal and limb nerves exert powerful control on trigeminal reflex pathways, probably via a common neural substrate. There is evidence that, in addition to any post-synaptic mechanism which might be operating, presynaptic control is a primary factor contributing to these changes.     

Blink reflex induced by controlled, ballistic mechanical impacts

The blink reflex was induced by a defined mechanical impact covering the range from light touch to a hard, painful stroke, and by an electrical current. In both modes of stimulation, the R3--but not the R2--thresholds were correlated with subjective pain thresholds, suggesting a connection between R3 and nociceptor activation. However, R3 magnitude did not increase systematically with increasing levels of subjectively felt pain. The R3, induced by painful impacts, habituated quickly and was strongly affected by attention. The functional significance of the R3 component is discussed.     

Enhanced gain of blink reflex responses to ipsilateral supraorbital nerve afferent inputs in patients with facial nerve palsy.

OBJECTIVES: Patients with peripheral facial palsy (PFP) may present with transient hyperkinetic movement disorders in the side contralateral to the paralysis. One possible cause of such enhanced motor activity is sensitization of reflex responses to afferent inputs from the unprotected cornea. We hypothesized that if this sensitization occurs, the size of the orbicularis oculi (OOc) responses induced by afferents from the ophthalmic branch of the paralyzed side would be larger than those induced by afferents from the contralateral side. METHODS: In 68 patients with complete PFP and in a group of 30 age-matched control subjects we recorded the response of the OOc muscle of one side to electrical stimulation of the supraorbital nerve of both sides, and calculated the ratio between R2c and R2 (R2c/R2). RESULTS: The mean R2c/R2 ratio was significantly larger in patients than in control subjects (unpaired t test, P<0.05). Larger R2c than R2 responses were observed in 23.1% of control subjects and in 80.9% of patients (chi(2)=13.3, P<0.01). CONCLUSIONS: Our results suggest that patients with PFP have an enhanced blink reflex gain to inputs from the paralyzed side compared to those of the non-paralyzed side. Sensitization of the blink reflex polysynaptic pathways to inputs carried by afferent fibers from the ophthalmic branch of the paralyzed side can play a role in inducing an abnormal facial motor behavior after PFP.     

Unmasking of the trigemino-accessory reflex in accessory facial anastomosis

OBJECTIVE: To evaluate the possible blink reflex responses in facial muscles reinnervated by the accessory nerve. METHOD: Eleven patients with a complete facial palsy were submitted to a surgical repair by an accessory facial nerve anastomosis (AFA). In this pathological group, blink reflex was studied by means of percutaneous electrical stimulation of the supraorbital nerve and recording from the orbicularis oculi muscle. A control group comprised seven normal people and seven patients with a complete Bell's facial palsy; in this group, responses on the sternocleidomastoideus (SCM) muscles were studied after supraorbital nerve stimulation. RESULTS: All the patients with AFA showed a consistent degree of facial reinnervation. Ten out of the 11 patients with AFA showed reflex responses; in six, responses were configured by a double component pattern, resembling the R1 and R2 components of the blink reflex; three patients had an R1-like response and one patient showed a unique R2 component. Mean values of latencies were 15.2 (SD 4.6) ms for the R1 and 85.3 (SD 9.6) ms for the R2. In the control group, eight out of 14 people had evidence of reflex responses in the SCM muscles; these were almost exclusively configured by a bilateral late component (mean latency 63.5 (SD15.9) ms) and only one of the subjects showed an early response at 11 ms. CONCLUSION: The trigemino-accessory reflex response in the pathological group was more complex and of a significantly higher incidence than in the control group. These differences could be tentatively explained by a mechanism of synaptic plasticity induced by the impairment of the efferent portion of the reflex. This could unmask the central linking between the trigeminal and the accessory limbs of the reflex. The findings described could be a demonstration of neurobionomic function in the repairing process of the nervous system.     

Maturation of blink reflex in children

The blink reflex was examined in 57 subjects aged from neonate to adult in the alert state. The ipsilateral late response (R2) was elicited in all subjects and considered most suitable to evaluate maturational changes of the blink reflex. In a few subjects older than 3 years and of adults, the ipsilateral early response (R1) was difficult to observe. The contralateral late response (R2') could not be obtained in 32% of neonates and infants. From the observation about developmental change of an interference pattern, a latency shortening of R2 and a latency difference between R2' and R2, the blink reflex in children may be considered as mature at no later than 5 years of age. In addition, the R2 latency tended to increase temporarily through 1 or 2 years from late infancy. The reflex circuit evaluated by the blink reflex in children may partially change its makeup after the early infantile period and is almost fully mature at no later than 5 years.     

Electrically and mechanically elicited blink reflexes in infants and children--maturation and recovery curves of blink reflex.

We studied the electrically and mechanically elicited blink reflexes in 2 groups of subjects, i.e., 237 newborn infants, 25-41 weeks of conceptional age, and 74 children, 1 month-12 years of age. In infants after 25 weeks of conceptional age we could usually induce the early response (R1) and ipsilateral late response (R2), while the contralateral late response (R2') of the electrical blink reflex became apparent after 33 weeks of conceptional age and the frequency of the appearance of R2' reached more than 60% after 38 weeks of conceptional age. After 7 months of age, R2' was usually observed. The R1 latency in full-term newborns was close to adult values, while the R2 and R2' latencies reached adult values at 7-12 years. After 1 year of age the latency of the R2 mechanical blink reflex had a tendency to be shorter than that of the electrical blink reflex. Under 35 weeks of conceptional age, the recovery curves of the blink reflex were considerably different from those of full-term infants, and premature infants showed little or no evidence of inhibition. These results indicate the absence of inhibitory interneurones in premature infants.     

Orbicularis oculi responses to stimulation of nerve afferents from upper and lower limbs in normal humans

A brief mechanical or electrical stimulus to peripheral nerve afferents from the upper and lower limbs elicited a small and inconsistent EMG response of the orbicularis oculi muscles. This response was facilitated when the stimuli were delivered at fixed leading time intervals, of 45–300 ms, with respect to a supraorbital nerve electrical stimulus. Also, the peripheral nerve stimulus modified the conventional blink reflex responses, inducing facilitation of R1 and inhibition of R2. These results suggest a complex processing of sensory inputs from the face and the limbs at the brainstem, where they are probably integrated in a network of interneurons influencing the excitability of facial motoneurons.     

Partial restoration of blink reflex function after spinal accessory-facial nerve anastomosis.

Functional motor control requires perfect matching of the central connections of motoneurons with their peripheral inputs. It is not known, however, to what extent these central circuits are influenced by target muscles, either during development or after a lesion. Surgical interventions aimed at restoring function after peripheral nerve lesions provide an opportunity for studying this interaction in the mature human nervous system. A patient was studied in whom the spinal accessory nerve was anastomosed into a lesioned facial nerve, allowing voluntary contractions of the previously paralysed muscles. This procedure, in addition to replacing the facial neurons at peripheral synapses, allowed a new short latency trigeminospinal accessory reflex of the R1 blink reflex type to be demonstrated, implying that trigeminal neurons had sprouted towards spinal accessory motoneurons over a distance of at least 1 cm. These results show an unexpected influence of the periphery in remodelling central connectivity in humans. The motoneuronal excitability for this R1 reflex response was therefore studied to compare the convergent properties of facial motoneurons (normal side) with those of the spinal accessory motoneurons (operated side) using a classic double shock technique with variable interstimulus intervals (conditioning test stimulus). On the normal side, conditioning stimuli (to the ipsilateral or contralateral infraliminar supraorbital nerve) produced a clearcut facilitation of the R1 blink reflex when the interstimulus interval was 30-80 ms. By contrast, a similar procedure had no effect on the R1 blink reflex mediated via the trigeminal-spinal accessory reflex arc. These data indicate that despite the heterotopic sprouting of some axons from neurons in the XIth nucleus, motoneurons involved in the newly formed reflex arc remain totally inexcitable by other trigeminal afferents and seem unable to ensure a physiological functioning of the normal blink reflex. Thus the functional relevance of the recovered R1 blink response remains unclear.     

A study of blink reflex in person with severely handicapped]

1) We evaluated blink reflex from 50 cases of severe handicapped. 7 cases (14%) had normal blink reflex. Abnormality of prolonged latency or no response of blink reflex was much more easily seen on R2 and R2' than R1, and dysfunction of spinal trigeminal complex or bulbar reticular formation might be existed in those cases. 2) We found abnormal blink reflex had some relationship with mental disturbance or bulbar function. Result of ABR and head CT also suggested that some kinds of cerebral factors might influenced to blink reflex of severe handicapped cases. 3) Blink reflex was one of the useful records for severe handicapped patients to evaluated underline pathogenesis of brain stem function.     

Anatomical observations on the afferent projections to the retractor bulbi motoneuronal cell group and other pathways possibly related to the blink reflex in the cat

In the cat retractor bulbi (RB) muscle reflexively retracts the eye ball into the orbit. This reflex action is called the nictitating membrane response which, together with the reflex contraction of the orbicularis oculi muscle, constitutes the blink reflex. The retractor bulbi (RB) motoneuronal nucleus is a small cell group located in the lateral tegmentum of the caudal pons, just dorsal to the superior olivary complex. The nucleus is identical to the accessory abducens nucleus and sends its fibers through the abducens nerve. Autoradiographical tracing results indicate that the RB nucleus receives some fibers from the principal and rostral spinal trigeminal nuclei and from the dorsal red nucleus and dorsally adjoining tegmentum. The same areas project to the intermediate facial subnucleus, containing motoneurons innervating the orbicularis oculi muscle. It is suggested that the trigeminal projections take part in the anatomical framework for the R1 component of the blink reflex. Two other brainstem areas i.e.: a portion of the caudal pontine ventrolateral tegmental field and the medullary medial tegmentum at the level of the hypoglossal nucleus were also found to project to the RB motoneuronal cell group and to the intermediate facial subnucleus. These projections were much stronger than those derived from the trigeminal nuclei and red nucleus. Moreover, the medullary premotor area projects not only to the blink motoneuronal cell groups but also to the pontine premotor area. It is suggested that both areas are involved in the R2 blink reflex component. The medullary blink premotor area receives afferents especially from oculomotor control structures in the reticular formation of the brainstem while the pontine blink premotor area receives afferents from the olivary pretectal nucleus and/or the nucleus of the optic tract and from the dorsal red nucleus and its dorsally adjoining area. Because the oculomotor control structures in the reticular formation (by way of the superior colliculus) and the red nucleus receive afferents from trigeminal nuclei, they may play an important role in tactually induced reflex blinking, while the pretectum could take part in the neuronal framework of the visually induced blink reflex.     

Anatomical observation on the afferent projections to the retractor bulbi motoneuronal cell group and other pathways possibly related to the blink reflex in the cat

In the cat the retractor bulbi (RB) muscle reflexively retracts the eye ball into the orbit. This reflex action is called the nictitating membrane response which, together with the reflex contraction of the orbicularis oculi muscle, constitutes the blink reflex. The retractor bulbi (RB) motoneuronal nucleus is a small cell group located in the lateral tegmentum of the caudal pons, just dorsal to the superior olivary complex. The nucleus is identical to the accessory abducens nucleus and sends its fibers through the abducens nerve. Autoradiographical tracing results indicate that the RB nucleus receives some fibers from the principal and rostral spinal trigeminal nuclei and from the dorsal red nucleus and dorsally adoining tegmentum. The same areas project to the intermediate facial subnucleus, containing motoneurons innervating the orbicularis oculi muscle. It is suggested that the trigeminal projections take part in the anatomical framework for the R1 component of the blink reflex. Two other brainstem areas i.e.: a portion of the caudal pontine ventrolateral tegmental field and the medullary media tegmentum at the level of the hypoglossal nucleus were also found to project to the RB motoneuronal cell group and to the intermediate facial subnucleus. These projections were much stronger than those derived from the trigeminal nuclei and red nucleus. Moreover, the medullary premotor area projects not only to the blink motoneuronal cell groups but also to the pontine premotor area. It is suggested that both areas are involved in the R2 blink reflex component. The medullary blink premotor area receives afferents especially from oculomotor control structures in the reticular formation of the brainstem while the pontine blink premotor area receives afferents from the olivary pretectal nucleus and/or the nucleus of the optic tract and from the dorsal red nucleus and its dorsally adjoining area. Because the oculomotor control structures in the reticular formation (by way of the superior colliculus) and the red nucleus receive afferents from trigeminal nuclei, they may play an important role in tactually induced reflex blinking, while the pretectum could take part in the neuronal framework of the visually induced blink reflex.     

Interaction of nociceptive and non-nociceptive cutaneous afferents from foot sole in common reflex pathways to tibialis anterior motoneurones in humans

In six healthy subjects, the reflex responses of the tibialis anterior muscle (TA) to stimulation of the cutaneous afferents arising from plantar foot, were studied at rest and during different levels of steady voluntary contraction of the TA. At rest, the threshold of the response and the threshold of subjective pain sensation coincided. The mean latency of this TA nociceptive response was 84.7 ms. Steady voluntary contractions of the TA, which was increased progressively from 3% to 15% of the maximum voluntary contraction, produced a significant and parallel reduction in the threshold and latency of the response: at 15%, the mean latency was about 26 ms shorter than at rest and its threshold was about half (i.e. below the pain threshold). The conduction velocity of the afferents responsible for TA response at rest was within the range of A-δ pain afferents (mean 27.4 m/s), whereas during voluntary contraction it was within the A-β fibre range (mean 45.1 m/s). This suggests that descending command makes the discharge of low-threshold, fast-conducting fibres sufficient for reflex activation of TA motoneurones (MNs). Central delay (about 4 ms) and MN recruitment order (according to the size principle) were found to be the same for both nociceptive and non-nociceptive TA reflex responses. Finally, experiments of spatial summation revealed an interaction between nociceptive and non-nociceptive inputs at a premotoneuronal level. It is therefore proposed that nociceptive and non-nociceptive cutaneous afferents arising from the foot sole use the same short-latency spinal pathway to contact TA MNs and that their relative contribution to its segmental activation is contingent upon descending command.     

The electrically elicited startle blink reflex in patients with schizophrenia: A threshold study of different reflex components

The electrically elicited blink reflex consists of three components (R1, R2, R3). In humans the excitability of these components is influenced by attentional states. In particular, distraction from the stimulus leads to facilitation of the bilateral R2 and R3. The present study was performed in order to investigate the excitability of the different components of the electrically evoked blink reflex in 13 patients with schizophrenia and 13 normal controls under standard conditions. Therefore, the thresholds of the distinct components were determined without any inhibitory or facilitatory procedure. There was no significant difference in R1 and R2 thresholds between patients and controls. In contrast, the R3 threshold was significantly reduced in schizophrenic patients (R3 threshold = 17.5 mA in normal subjects, 10.5 mA in patients, p = 0. 0001). In recent studies the R3 magnitude was found to be highly susceptible to changes in the attentional state of normal subjects. The lower threshold of R3 in patients with schizophrenia might therefore be a neurophysiological marker of attentional dysfunctions in schizophrenia.