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

doi:10.1016/S1388-2457(99)00295-3

Clinical Neurophysiology

Volume 111, Issue 3, 1 March 2000, Pages 413-416

https://doi.org/10.1016/S1388-2457(99)00295-3 Get rights and content

Abstract

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.

Introduction

The blink reflex (BR) is a trigeminofacial brain-stem reflex. After electrical stimulation of the supraorbital nerve 3 components can be distinguished: an oligosynaptic ipsilateral pontine R1 component (onset latency 11 ms) and two polysynaptic bilateral medullary components R2 and R3 (onset latencies 33 and 84 ms) (Ellrich and Hopf, 1996). Whereas R1 and R2 can be elicited by innocuous mechanical stimuli, only R2 but not R1 can also be elicited by selective activation of nociceptors using laser radiant heat stimuli suggesting an involvement of nociceptive neurones of the medullary dorsal horn in the mediation of R2 (Ellrich et al., 1997). The R2 was inhibited by remote painful heat stimuli and facilitated by homotopically applied painful heat demonstrating that R2 is mainly mediated via wide dynamic range (WDR) interneurones in the medullary dorsal horn, whereas R1 is relayed by low threshold mechanoreceptive (LTM) neurones (Sessle et al., 1986, Ellrich and Treede, 1998, Ellrich et al., 1998). Two approaches have been followed so far to study trigeminal brain-stem nociception and transmission in humans more selectively: electrical or mechanical eliciting of the corneal reflex (Cruccu et al., 1991, Cruccu et al., 1997) because of the purely nociceptive nature of its afferents and the use of noxious heat stimuli to elicit the BR (Ellrich et al., 1997). For extracranial sites intracutaneous low current intensity stimulation has been employed to selectively depolarise superficial nociceptive cutaneous fibres (Bromm and Meier, 1984). In the present study we investigated whether the use of a modified surface electrode allows noninvasive and more selective stimulation of superficial nociceptive fibres in the territory of the supraorbital nerve to elicit the BR.

Section snippets

Materials and methods

The subjects were 10 healthy volunteers (3 males, 7 females, age range 21–33 years) who gave informed consent before testing. This study was approved of by the local ethics committee.

Results

Stimulation with NE elicited a dull, paraestethic and slightly painful sensation at stimulus intensities of 10–15 mA. CE in contrast, produced a pin-prick-like pain between 0.4 and 2.0 mA. Stimulation with CE at these low intensities elicited no R1 response.

Using stimulation with CE at baseline individual sensory thresholds (Is) were: 0.34±0.19 (SD) (0.2–0.6) mA; pain thresholds (Ip) 0.54±0.19 (0.2–0.8) mA. After LA Is increased to 1.34±0.29 (1.0–1.8) mA and the sensation of sharp pain after CE

Discussion

This study investigated a different electrode type (CE) to electrically elicit the BR. In contrast to normal electrical stimulation (NE) CE produces a sharp pin prick like pain. This sensation together with thermaesthesia is abolished after local anaesthesia. At the same time the R2 component after CE is diminished by more than 90%. This indicates that the majority of A-delta- and C-fibres were blocked by the superficial application of the LA after 40 min. In contrast sensation to touch was

References (9)

G. Cruccu et al.
Nociceptive quality of the orbicularis oculi reflexes as evaluated by distinct opiate- and benzodiazepine-induced changes in man
Brain Res
(1991)
G. Cruccu et al.
Corneal reflex responses to mechanical and electrical stimuli in coma and narcotic analgesia in humans
Neurosci Lett
(1997)
J. Ellrich et al.
The R3 component of the blink reflex: normative data and application in spinal lesions
Electroenceph clin Neurophysiol
(1996)
J. Ellrich et al.
Characterization of blink reflex interneurons by activation of diffuse noxious inhibitory controls in man
Brain Res
(1998)

There are more references available in the full text version of this article.

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