Headache is classified as either Primary or Secondary Headache.1 Primary Headaches are those headache and migraine conditions with unknown pathophysiology. Secondary Headache comprises headache arising from a recognised and accepted cause, i.e. secondary to a known source. Cervicogenic Headache (CeH) is classified as a secondary headache i.e. headache secondary to a cervical lesion.1
Elementary neuro anatomy2-7 dictates, and substantial evidence7-11 demonstrates cervical afferents are not only a key player in head pain, but a potential source of the sensitisation of the trigemino cervical nucleus (TCN), the underlying disorder in migraine,7,12-14 if not, in other Primary Headache conditions.13-16
However, the existence of CeH is debated,17,18 (because) and currently there is no identifiable pathology i.e. there no validated lesions for CeH.17,18 Thus, CeH suffers the same fate as those of Primary Headache conditions, for whilst in theory, the pathophysiology of CeH is recognised, there are no bona fide, accepted lesions initiating the physiological process.
But… does there need to be evidence of a macroscopic lesion for noxious cervical afferents to be instrumental in not only CeH, but also as a sensitising source of the TCN in Primary Headache?
As in humans, histological studies of zygapophyseal joints in rats and goats have identified nociceptive nerve fibres in the joint’s capsular ligament.19-21 Mechanical hyperalgesia or allodynia represents enhanced nociceptive processing and as such is commonly used as an indicator of pain outcomes in animal studies.22,23
A substantial body of evidence from animal models has demonstrated the development of mechanical hyperalgesia (pain) from controlled, non injurious loading of the zygapophyseal joint capsule.22-33
These results imply that zygapophyseal joint19,34,35 mediated spinal hyperexcitability, plasticity of dorsal horn neuronal activity and pain,28,29,31 occur in response to abnormal alterations in fibre patterns of the capsule’s collagen matrix during loading occurring at or preceding capsular tolerance.36
Pathophysiological effects identified in mechanistic studies of the zygapophyseal joint in animal studies can be extrapolated to human pain processes.37-39 In particular, animal studies indicate that nociceptive afferent information from zygapophyseal joints contribute to central sensitisation; moreover, when considered with the ameliorating effect of anaesthetising40-53 or neurotomy54-57 of the medial branch of the third occipital nerve in humans, animal data provide a compelling argument for cervical zygapophyseal joints as a source of neck pain and/or headache.
Furthermore, a significant body (of animal research) involving noxious intervention of cervical musculature demonstrating sensitisation of the Brainstem/TCN provides additional support for cervical afferent sensitisation of the TCN.58-62
The fact that headache related neurophysiological phenomena result from non-injurious loading of the zygapophyseal joint capsule has significant implications. Not the least is that these findings are incongruent with the biomechanical premise that the degree of symptoms would be proportional to magnitude of soft tissue loading.63,64
Accordingly, there is general agreement that conventional medical imaging lacks sensitivity for capsular and intra-articular injuries of the spine.49,52-54,56,57,63,65,66 Consequently, computed tomography (CT) and magnetic resonance imaging (MRI) are not appropriate tests to rule out pathology.49,56,57,63,65,66 Instead, identifying lesions is likely to require more sophisticated and specialised methods. For example, in a positron emission tomography (PET) study, tracer uptake in proximity to the second cervical vertebra was significantly greater in Chronic Whiplash Associated Headache (CWAH) patients than controls, indicating local persistent peripheral tissue inflammation.67
Secondly, and conspicuously in relation to whiplash (and therefore implicitly cervical) disorders, the inability of customary medical imaging to identify pathology implies that the source of patients’ symptomatology is not always clinically detectable;52-54,56,66,68 i.e. the absence of extensive, conspicuous zygapophyseal joint capsular damage does not rule out nociceptive (symptomatic) relevance.49,52,63
Perhaps this explains why associated cervical symptoms are absent in some with CeH; 25000 hours of the author’s clinical experience suggests associated cervical symptoms are not a pre-requisite for cervical involvement.
Yes… CeH is a Secondary Headache, secondary to disturbed function of structures supplied by C1-3 cervical nerves, which, with rapid advances in technology of medical investigative techniques, are likely to demonstrate…
Just because you cannot see it, does not mean ‘it does not exist’
In the meantime, clinical experience and research would suggest that reproduction and resolution of customary head pain as the examination technique is sustained, remains the most accurate and cost effective determination of CeH or, relevancy of cervical afferents as the source of sensitisation of the TCN in Primary Headache.11
- Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. Jan 2018;38(1):1-211.
- Bogduk N. The anatomical basis for cervicogenic headache. J Manipulative Physiol Ther. Jan 1992;15(1):67-70.
- Kerr FW. Structural relation of the trigeminal spinal tract to upper cervical roots and the solitary nucleus in the cat. Exp Neurol. Aug 1961;4:134-148.
- Kerr FW, Olafson RA. Trigeminal and cervical volleys. Convergence on single units in the spinal gray at C-1 and C-2. Arch Neurol. Aug 1961;5:171-178.
- Piovesan EJ, Kowacs PA, Oshinsky ML. Convergence of cervical and trigeminal sensory afferents. Curr Pain Headache Rep. Oct 2003;7(5):377-383.
- Busch V, Jakob W, Juergens T, Schulte-Mattler W, Kaube H, May A. Functional connectivity between trigeminal and occipital nerves revealed by occipital nerve blockade and nociceptive blink reflexes. Cephalalgia. Jan 2006;26(1):50-55.
- Bartsch TGP. Anatomy and physiology of pain referral in primary and cervicogenic headache disorders. Headache Curr. 2005;2:42-48.
- Goadsby PJ, Knight YE, Hoskin KL. Stimulation of the greater occipital nerve increases metabolic activity in the trigeminal nucleus caudalis and cervical dorsal horn of the cat. Pain. Oct 1997;73(1):23-28.
- Piovesan EJ, Kowacs PA, Tatsui CE, Lange MC, Ribas LC, Werneck LC. Referred pain after painful stimulation of the greater occipital nerve in humans: evidence of convergence of cervical afferences on trigeminal nuclei. Cephalalgia. Mar 2001;21(2):107-109.
- Busch V, Jakob W, Juergens T, Schulte-Mattler W, Kaube H, May A. Occipital nerve blockade in chronic cluster headache patients and functional connectivity between trigeminal and occipital nerves. Cephalalgia. Nov 2007;27(11):1206-1214.
- Watson DH, Drummond PD. Cervical referral of head pain in migraineurs: effects on the nociceptive blink reflex. Headache. Jun 2014;54(6):1035-1045.
- Sandrini G, Proietti Cecchini A, Milanov I, Tassorelli C, Buzzi MG, Nappi G. Electrophysiological evidence for trigeminal neuron sensitization in patients with migraine. Neurosci Lett. Jan 14 2002;317(3):135-138.
- Milanov I, Bogdanova D. Trigemino-cervical reflex in patients with headache. Cephalalgia. Feb 2003;23(1):35-38.
- Nardone R, Ausserer H, Bratti A, et al. Trigemino-cervical reflex abnormalities in patients with migraine and cluster headache. Headache. Apr 2008;48(4):578-585.
- Nardone R, Tezzon F. The trigemino-cervical reflex in tension-type headache. Eur J Neurol. May 2003;10(3):307-312.
- Varlibas A, Erdemoglu AK. Altered trigeminal system excitability in menstrual migraine patients. J Headache Pain. Aug 2009;10(4):277-282.
- Becker WJ. Cervicogenic headache: evidence that the neck is a pain generator. Headache. Apr 2010;50(4):699-705.
- Vincent MB. Cervicogenic headache: the neck is a generator: con. Headache. Apr 2010;50(4):706-709.
- Inami S, Shiga T, Tsujino A, Yabuki T, Okado N, Ochiai N. Immunohistochemical demonstration of nerve fibers in the synovial fold of the human cervical facet joint. J Orthop Res. Jul 2001;19(4):593-596.
- Ohtori S, Takahashi K, Chiba T, Yamagata M, Sameda H, Moriya H. Sensory innervation of the cervical facet joints in rats. Spine (Phila Pa 1976). Jan 15 2001;26(2):147-150.
- Yamashita T, Cavanaugh JM, el-Bohy AA, Getchell TV, King AI. Mechanosensitive afferent units in the lumbar facet joint. J Bone Joint Surg Am. Jul 1990;72(6):865-870.
- Lee KE, Davis MB, Mejilla RM, Winkelstein BA. In vivo cervical facet capsule distraction: mechanical implications for whiplash and neck pain. Stapp Car Crash J. Nov 2004;48:373-395.
- Lee KE, Winkelstein BA. Joint distraction magnitude is associated with different behavioral outcomes and substance P levels for cervical facet joint loading in the rat. J Pain. Apr 2009;10(4):436-445.
- Lee KE, Thinnes JH, Gokhin DS, Winkelstein BA. A novel rodent neck pain model of facet-mediated behavioral hypersensitivity: implications for persistent pain and whiplash injury. J Neurosci Methods. Aug 30 2004;137(2):151-159.
- Quinn KP, Winkelstein BA. Cervical facet capsular ligament yield defines the threshold for injury and persistent joint-mediated neck pain. J Biomech. 2007;40(10):2299-2306.
- Lee KE, Davis MB, Winkelstein BA. Capsular ligament involvement in the development of mechanical hyperalgesia after facet joint loading: behavioral and inflammatory outcomes in a rodent model of pain. J Neurotrauma. Nov 2008;25(11):1383-1393.
- Winkelstein BA, Santos DG. An intact facet capsular ligament modulates behavioral sensitivity and spinal glial activation produced by cervical facet joint tension. Spine (Phila Pa 1976). Apr 15 2008;33(8):856-862.
- Dong L, Winkelstein BA. Simulated whiplash modulates expression of the glutamatergic system in the spinal cord suggesting spinal plasticity is associated with painful dynamic cervical facet loading. J Neurotrauma. Jan 2010;27(1):163-174.
- Quinn KP, Dong L, Golder FJ, Winkelstein BA. Neuronal hyperexcitability in the dorsal horn after painful facet joint injury. Pain. Nov 2010;151(2):414-421.
- Dong L, Smith JR, Winkelstein BA. Ketorolac reduces spinal astrocytic activation and PAR1 expression associated with attenuation of pain after facet joint injury. J Neurotrauma. May 15 2013;30(10):818-825.
- Kras JV, Dong L, Winkelstein BA. The prostaglandin E2 receptor, EP2, is upregulated in the dorsal root ganglion after painful cervical facet joint injury in the rat. Spine (Phila Pa 1976). Feb 1 2013;38(3):217-222.
- Kras JV, Dong L, Winkelstein BA. Increased interleukin-1alpha and prostaglandin E2 expression in the spinal cord at 1 day after painful facet joint injury: evidence of early spinal inflammation. Spine (Phila Pa 1976). Feb 1 2014;39(3):207-212.
- Crosby ND, Gilliland TM, Winkelstein BA. Early afferent activity from the facet joint after painful trauma to its capsule potentiates neuronal excitability and glutamate signaling in the spinal cord. Pain. Sep 2014;155(9):1878-1887.
- McLain RF. Mechanoreceptor endings in human cervical facet joints. Spine (Phila Pa 1976). Mar 1 1994;19(5):495-501.
- Kallakuri S, Singh A, Lu Y, Chen C, Patwardhan A, Cavanaugh JM. Tensile stretching of cervical facet joint capsule and related axonal changes. Eur Spine J. Apr 2008;17(4):556-563.
- Quinn KP, Bauman JA, Crosby ND, Winkelstein BA. Anomalous fiber realignment during tensile loading of the rat facet capsular ligament identifies mechanically induced damage and physiological dysfunction. J Biomech. Jul 20 2010;43(10):1870-1875.
- Mogil JS. Animal models of pain: progress and challenges. Nat Rev Neurosci. Apr 2009;10(4):283-294.
- Graven-Nielsen T, Mense S. The peripheral apparatus of muscle pain: evidence from animal and human studies. Clin J Pain. Mar 2001;17(1):2-10.
- Arendt-Nielsen L, Graven-Nielsen T. Translational musculoskeletal pain research. Best Pract Res Clin Rheumatol. Apr 2011;25(2):209-226.
- Barnsley L, Lord SM, Wallis BJ, Bogduk N. The prevalence of chronic cervical zygapophysial joint pain after whiplash. Spine (Phila Pa 1976). Jan 1 1995;20(1):20-25; discussion 26.
- Lord SM, Barnsley L, Wallis BJ, Bogduk N. Chronic cervical zygapophysial joint pain after whiplash. A placebo-controlled prevalence study. Spine (Phila Pa 1976). Aug 1 1996;21(15):1737-1744; discussion 1744-1735.
- Lord SM, Barnsley L, Wallis BJ, Bogduk N. Third occipital nerve headache: a prevalence study. J Neurol Neurosurg Psychiatry. Oct 1994;57(10):1187-1190.
- Bogduk N, Aprill C. On the nature of neck pain, discography and cervical zygapophysial joint blocks. Pain. Aug 1993;54(2):213-217.
- Bogduk N, Marsland A. The cervical zygapophysial joints as a source of neck pain. Spine (Phila Pa 1976). Jun 1988;13(6):610-617.
- Aprill C, Bogduk N. The prevalence of cervical zygapophyseal joint pain. A first approximation. Spine (Phila Pa 1976). Jul 1992;17(7):744-747.
- Schofferman J, Bogduk N, Slosar P. Chronic whiplash and whiplash-associated disorders: an evidence-based approach. J Am Acad Orthop Surg. Oct 2007;15(10):596-606.
- Third-nerve headache. Lancet. Aug 16 1986;2(8503):374.
- Gobel H EJ, ed Disorders of of the skull and cervical spine. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2000. Olesen J T-HP, Welch KMA., ed.
- Verhagen AP, Lewis M, Schellingerhout JM, et al. Do whiplash patients differ from other patients with non-specific neck pain regarding pain, function or prognosis? Man Ther. Oct 2011;16(5):456-462.
- Speldewinde GC, Bashford GM, Davidson IR. Diagnostic cervical zygapophyseal joint blocks for chronic cervical pain. Med J Aust. Feb 19 2001;174(4):174-176.
- Manchukonda R, Manchikanti KN, Cash KA, Pampati V, Manchikanti L. Facet joint pain in chronic spinal pain: an evaluation of prevalence and false-positive rate of diagnostic blocks. J Spinal Disord Tech. Oct 2007;20(7):539-545.
- Manchikanti L, Manchikanti KN, Cash KA, Singh V, Giordano J. Age-related prevalence of facet-joint involvement in chronic neck and low back pain. Pain Physician. Jan 2008;11(1):67-75.
- Manchikanti L, Singh V, Pampati V, Damron KS, Beyer CD, Barnhill RC. Is there correlation of facet joint pain in lumbar and cervical spine? An evaluation of prevalence in combined chronic low back and neck pain. Pain Physician. Oct 2002;5(4):365-371.
- Lord SM MG, Bogduk N. Percutaneous radio frequency neurotomy of the cervicla medial branches: a validated treatment for cervicla zygapophyseal joint pain. . Neurosurg Q. 1998(8):288-308.
- McDonald GJ, Lord SM, Bogduk N. Long-term follow-up of patients treated with cervical radiofrequency neurotomy for chronic neck pain. Neurosurgery. Jul 1999;45(1):61-67; discussion 67-68.
- Sapir DA, Gorup JM. Radiofrequency medial branch neurotomy in litigant and nonlitigant patients with cervical whiplash: a prospective study. Spine (Phila Pa 1976). Jun 15 2001;26(12):E268-273.
- Govind J, King W, Bailey B, Bogduk N. Radiofrequency neurotomy for the treatment of third occipital headache. J Neurol Neurosurg Psychiatry. Jan 2003;74(1):88-93.
- Hu JW, Yu XM, Vernon H, Sessle BJ. Excitatory effects on neck and jaw muscle activity of inflammatory irritant applied to cervical paraspinal tissues. Pain. Nov 1993;55(2):243-250.
- Makowska A, Panfil C, Ellrich J. Long-term potentiation of orofacial sensorimotor processing by noxious input from the semispinal neck muscle in mice. Cephalalgia. Feb 2005;25(2):109-116.
- Makowska A, Panfil C, Ellrich J. ATP induces sustained facilitation of craniofacial nociception through P2X receptors on neck muscle nociceptors in mice. Cephalalgia. Jun 2006;26(6):697-706.
- Ellrich J, Makowska A. Nerve growth factor and ATP excite different neck muscle nociceptors in anaesthetized mice. Cephalalgia. Nov 2007;27(11):1226-1235.
- Vernon H, Sun K, Zhang Y, Yu XM, Sessle BJ. Central sensitization induced in trigeminal and upper cervical dorsal horn neurons by noxious stimulation of deep cervical paraspinal tissues in rats with minimal surgical trauma. J Manipulative Physiol Ther. Sep 2009;32(7):506-514.
- Elliott JM, Courtney DM, Rademaker A, Pinto D, Sterling MM, Parrish TB. The Rapid and Progressive Degeneration of the Cervical Multifidus in Whiplash: An MRI Study of Fatty Infiltration. Spine (Phila Pa 1976). Jun 15 2015;40(12):E694-700.
- Bogduk N. On cervical zygapophysial joint pain after whiplash. Spine (Phila Pa 1976). Dec 1 2011;36(25 Suppl):S194-199.
- Rodriquez AA, Barr KP, Burns SP. Whiplash: pathophysiology, diagnosis, treatment, and prognosis. Muscle Nerve. Jun 2004;29(6):768-781.
- Lord SM, Barnsley L, Wallis BJ, McDonald GJ, Bogduk N. Percutaneous radio-frequency neurotomy for chronic cervical zygapophyseal-joint pain. N Engl J Med. Dec 5 1996;335(23):1721-1726.
- Linnman C, Appel L, Fredrikson M, et al. Elevated [11C]-D-deprenyl uptake in chronic Whiplash Associated Disorder suggests persistent musculoskeletal inflammation. PLoS One. 2011;6(4):e19182.
- Elliott JM. Are there implications for morphological changes in neck muscles after whiplash injury? Spine (Phila Pa 1976). Dec 1 2011;36(25 Suppl):S205-210.