Abstract
Cranial sensory innervation is supplied mainly by the trigeminal nerves and by the first cervical nerves. Excitatory and inhibitory interactions among those nerve roots may occur in a mechanism called nociceptive convergence, leading to loss of somato-sensory spatial specificity. Three volunteers in an experimental trial had sterile water injected over their greater occipital nerve on one side of the neck. Pain intensity was evaluated 10, 30 and 120 s after the injection. Two of the patients reported intense pain. Trigeminal autonomic features, suggestive of parasympathetic activation, were seen associated with trigeminally distributed pain. These data add to and reinforce previous evidence of convergence of cervical afferents on the trigeminal sensory circuit.
Introduction
Cranial sensation is provided by afferents of the trigeminal nerve and the first cervical roots, intermingled in association or dissociation (1). However, convergence of pain has not been studied in detail in humans, since most descriptions refer to case reports in which this type of phenomenon is secondary to vascular or tumoral aetiology (2). For ethical reasons, some studies to clarify pain mechanisms in humans cannot be routinely carried out. This paper refers to a unique opportunity to study the projections of the greater occipital nerve (GON) through painful stimuli.
Patients and methods
Three of the patients presented here had already been studied in previous research (3). All the patients included had right side-locked migraine attacks. Injections over the GON were carried out transcutaneously according to the procedure described by Vital (4, 5), only on the right side. All patients received 2 ml of sterile water (SW) injected over the right GON. The intensity of the pain was evaluated through a visual analogue scale (VAS) (6), during and 10, 30 and 120 s after the injection. Pain was classified as low, moderate and severe, for VAS measurements ranging from 0 to 30 mm, 31–52 mm and greater than 52 mm, respectively (7). The patients also drew their sites of perceived pain on a sketch of the head (Fig. 1).
Distribution of the pain sensory symptoms.
Results
Ten seconds after the injection, the patients developed severe pain at the site of injection. For patient No. 2, the pain was kept limited to her right GON territory, gradually subsiding. The other two patients had referred pain, projecting not only over their right GON territories but also over the areas innervated by the first branch of the trigeminal nerve (V1) on the same side of the head.
Ten seconds after the injection, patient No. 1 suffered severe pain, involving not only the territory of the right GON but also her right supraorbital area. Those pains reached a severe, excruciating intensity 30 s after the injections. Two minutes after the injection the V1 pain had subsided completely but the pain in the GON territory persisted, although moderate in intensity. Facial flushing, conjunctival injection and tearing on the same side of the head developed along with the pain and subsided after 1 min.
Patient No. 3, 10 s after the injection, had severe pain not only at his right GON, but also projecting to the territory of his right first trigeminal cutaneous innervation (v1), including the eyeball. Thirty seconds after the injection the pain was excruciating in both territories and was maintained in both areas for 2 min. Five minutes after the injection the V1 component subsided. Ipsilateral facial flushing, conjunctival injection and tearing also developed along with the pain and subsided after 60 s.
Patients 1 and 3 described their trigeminal pains as lancinating with intermingled paroxysms lasting approximately 2–3 s. For both it was perceived as more intense than the occipital pain. Right occipital pain lasted an average of 4 h and was the only pain in patient 2. Table 1 summarizes the distribution and evolution of the VAS scores of the three patients, from the infiltration until 2 min later.
Pain distribution and intensity
VAS, visual analogue scale; GON, greater occipital nerve; V1, first trigeminal branch; s, seconds.
Discussion
Cranial nociceptive volleys are perceived, processed and carried by highly specialized structures towards trigeminal nuclei cells in the pons, medulla oblongata and upper spinal cord (8). The trigeminal nuclei and the upper spinal cord posterior roots have a close anatomical and functional relationship, which leads to convergence of the posterior upper cervical roots on the nucleus trigeminalis caudalis and the dorsolateral nuclei of the upper cervical spinal cord (9, 10). Unilateral stimulation of the GON elicits pain in its territory and in areas innervated by other nerves, mainly in those pertaining to the ipsilateral first trigeminal branch (11–13). This convergence mechanism can be clinically appreciated in most forms of primary headache as in those headaches stimuli arising from the neck can trigger ipsilateral headaches projecting onto trigeminal territories (11). On the other hand, experimental studies on animals have shown that mechanical (14) and electrical (15) stimulation of intracranial vascular structures, such as the middle cerebral artery (in rats), the superior sagital sinus (in rats and in the macaca nemestrina) (15), and of the anterior and posterior cranial cavities, activates cells in the nucleus trigeminalis caudalis and/or the dorsal horn down to the C2 level (16). Perhaps some clinical correlates of these projections are the pain secondary to middle cerebral artery dilatation, that projects to trigeminal areas where migraine pain is most often experienced (17), and the occipital and neck pain that may be observed during migraine and cluster headache attacks (18, 19).
The symptoms presented by the patients can be attributed to activation of the delta-A group fibres (type III fibres) as those fibres are characterized by rapid synaptic responses of second order neurones in the dorsal horn (19). The short-lasting, lancinating pain, emerging approximately 10 s after the sterile water injection, associated with autonomic symptoms on the same side, suggests not only convergence to V1 nuclei, but also parasympathetic and/or antidromic trigeminal vascular activation. This autonomic activation echoes the clinical findings of some cephalalgias with trigeminal autonomic features, such as cervicogenic headache, chronic paroxysmal hemicrania and SUNCT syndrome, in which unilateral trigeminal pain, associated with ipsilateral parasympathetic activation, can be triggered by neck movements (20).
Intracutaneous sterile water injections have been reported to relieve acute labour pain and cervical pain in whiplash patients (21), but in some cases of secondary headache the sterile water injection is not effective (22).
Our findings support the existence, in humans, of convergence of cervical nociceptive projections to the trigeminal nuclei. Its relevance for the physiology of cranial sensation, as well as its role in primary headaches, is not fully known. Whether GON afferences converge only on the nucleus trigeminalis caudalis or on higher levels remains to be clarified.