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Unremitting head and neck pain (UHNP) is a commonly encountered phenomenon in Headache Medicine and may be seen in the setting of many well-defined headache types. The prevalence of UHNP is not clear, and establishing the presence of UHNP may require careful questioning at repeated patient visits. The cause of UHNP in some patients may be compression of the lesser and greater occipital nerves by the posterior cervical muscles and their fascial attachments at the occipital ridge with subsequent local perineural inflammation. The resulting pain is typically in the sub-occipital and occipital location, and, via anatomic connections between extracranial and intracranial nerves, may radiate frontally to trigeminal-innervated areas of the head. Migraine-like features of photophobia and nausea may occur with frontal radiation. Occipital allodynia is common, as is spasm of the cervical muscles. Patients with UHNP may comprise a subgroup of Chronic Migraine, as well as of Chronic Tension-Type Headache, New Daily Persistent Headache and Cervicogenic Headache. Centrally acting membrane-stabilizing agents, which are often ineffective for CM, are similarly generally ineffective for UHNP. Extracranially-directed treatments such as occipital nerve blocks, cervical trigger point injections, botulinum toxin and monoclonal antibodies directed at calcitonin gene related peptide, which act primarily in the periphery, may provide more substantial relief for UHNP; additionally, decompression of the occipital nerves from muscular and fascial compression is effective for some patients, and may result in enduring pain relief. Further study is needed to determine the prevalence of UHNP, and to understand the role of occipital nerve compression in UHNP and of occipital nerve decompression surgery in chronic head and neck pain.

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Challenges continue beyond the establishment of the presence of UHNP to the realms of diagnosis and treatment. The management of UHNP is unclear, in part because UHNP is generally not evaluated in clinical studies. There was no query regarding the presence of neck pain as a factor directly related to headache characteristic or frequency, or to headache reduction, in any of the clinical studies of the three commercially available monoclonal antibodies directed at calcitonin gene related peptide (CGRP), including erenumab [personal communication, Jason Skinner, Phd, Amgen], fremanezumab [personal communication, Michael Seminerio, PhD, Teva Pharmaceutical, or galcanezumab [Iman Mangum, Lilly USA], or in the clinical trials for botulinum toxin [Harsha Patel, PhD, Allergan]. Additionally, subjects with constant headache are typically excluded from clinical studies of botulinum toxin and of CGRP monoclonal antibodies, as such patients lack discrete episodes of headache that can be counted for statistical analysis [personal communication, Michael Seminerio, PhD, Teva Pharmaceutical; Jason Skinner, Phd, Amgen; Iman Mangum, Lilly USA; Harsha Patel, PhD, Allergan].

The etiology of pain in chronic headache, including UHNP, CM and CTTH, is not yet clear. While nociceptive activity of the meninges and the trigeminovascular system is well established, the underlying activators of these nociceptors is unclear. The etiology of neck pain is similarly unknown. Some authors have attributed the common occurrence of neck pain to the convergence of sensory afferents from the upper cervical region with trigeminal afferents in the trigeminal cervical complex [7]; this theory, however, remains unproven. The absence of imaging abnormalities of cervical bony and neural structures that are within the spatial resolution of current clinical MRI has further supported the concept that central processes involving upper cervical afferents along with trigeminal nociceptors is the cause of neck pain in headache. Thus, most of the research on the cause of headache pain has been directed at intracranial processes, such as central sensitization and activation of brainstem pathways [8], and the role of these central processes in migraine has accordingly become generally accepted and regarded as validated, even when the conclusions of research were not necessarily consistent with a causative, solely central process. For example, some findings in migraine that have been interpreted as suggestive of central causation, such as altered functional activity in the anterior cingulate cortex, prefrontal cortex, thalamus and somatosensory cortex [9], have also been reported in other chronic pain conditions, such as fibromyalgia [10]. Such findings may thus reflect alterations of pain processing that are common to many chronic pain conditions rather than indicating phenomena unique to migraine.

We speculate that while triptan agents may be effective for the acute exacerbations of frontal, trigeminally-mediated pain, the unremitting pain in the neck and occiput often does not respond to such acute interventions; nor does the UHNP generally respond well to centrally directed, membrane stabilizing agents such as anti-convulsants. Peripherally directed treatments such as steroid injections to the occiput in the form of trigger point injections or occipital nerve blocks, as well as botulinum toxin and monoclonal antibodies directed at CGRP, may provide temporary benefit for the UHNP caused by occipital nerve compression. Surgical decompression of the occipital nerves may provide more enduring relief of pain.

It is important and helpful to distinguish the symptoms of UHNP associated with ON compression from the condition of Occipital Neuralgia as defined in the ICHD [3]. Occipital Neuralgia is defined as pain that has two of the following three characteristics: [1] recurring in paroxysmal attacks lasting from seconds to minutes; [2] severe in intensity; [3] shooting, stabbing or sharp in quality. The pain is associated with dysesthesia and/or allodynia, and either tenderness to palpation of the nerve or its branches, or the presence of tender trigger points at the emergence of the GON. The pain must also be temporarily eased by an anesthetic block of the GON.

In our experience and those of other clinicians, Occipital Neuralgia is uncommon. There are some areas of overlap between the clinical presentation of ON compression and Occipital Neuralgia, however, as well as some areas of important difference. Areas of overlap of the two conditions include [1] the presence of allodynia and [2] tenderness to palpation of either the nerve or the soft tissue of the suboccipital space. Areas of difference include [1] the character of pain: most individuals with ON compression report their primary pain symptom to be tightness and pressure, not stabbing, sharp pain (such neuropathic symptoms are occasionally encountered in our [PB] experience, but they are almost always less frequent than the overwhelming pressure sensation); [2] the duration of the symptoms, which as noted repeatedly above, is generally unremitting in ON compression, and not in the paroxysmal attacks required for Occipital Neuralgia; and [3] the intensity of pain, which in ON compression is most often not severe, and may be mild to moderate on a typical day, as opposed to the severe intensity that is required for the diagnosis of Occipital Neuralgia. Finally, we find the response to ON blocks in ON compression (as proven by later response to surgical decompression) to be somewhat variable. While the majority of patients experience a reduction in pain, not all do, and some patients experience a provoked headache that may offset any eventual benefit from the block.

The cause is not entirely clear.[10] Risk factors include having a family history of the condition.[2] The areas of endometriosis bleed each month (menstrual period), resulting in inflammation and scarring.[1][2] The growths due to endometriosis are not cancer.[2] Diagnosis is usually based on symptoms in combination with medical imaging;[2] however, biopsy is the surest method of diagnosis.[2] Other causes of similar symptoms include pelvic inflammatory disease, irritable bowel syndrome, interstitial cystitis, and fibromyalgia.[1] Endometriosis is commonly misdiagnosed and females often report being incorrectly told their symptoms are trivial or normal.[9] Females with endometriosis see an average of seven physicians before receiving a correct diagnosis, with an average delay of 6.7 years between the onset of symptoms and surgically obtained biopsies, the gold standard for diagnosing the condition. This average delay places endometriosis at the extreme end of diagnostic inefficiency.[11]

A major symptom of endometriosis is recurring pelvic pain. The pain can range from mild to severe cramping or stabbing pain that occurs on both sides of the pelvis, in the lower back and rectal area, and even down the legs. The amount of pain a person feels correlates weakly with the extent or stage (1 through 4) of endometriosis, with some individuals having little or no pain despite having extensive endometriosis or endometriosis with scarring, while others may have severe pain even though they have only a few small areas of endometriosis.[17] The most severe pain is typically associated with menstruation. Pain can also start a week before a menstrual period, during and even a week after a menstrual period, or it can be constant. The pain can be debilitating and result in emotional stress.[18] Symptoms of endometriosis-related pain may include:

There are multiple causes of pain. Endometriosis lesions react to hormonal stimulation and may "bleed" at the time of menstruation. The blood accumulates locally if it is not cleared shortly by the immune, circulatory, and lymphatic system. This may further lead to swelling, which triggers inflammation with the activation of cytokines, which results in pain. Another source of pain is the organ dislocation th