Category: Uncategorized

Low Back Pain: Pathophysiology, Mechanisms, and Pain Generators

Low back pain (LBP) is the most common musculoskeletal condition affecting the adult population and a leading cause of disability worldwide, with a prevalence of 84%.1 Chronic LBP has a significant impact on functional capacity and occupational activities, is a major cause of absenteeism, and represents a major social and economic burden.1  One study estimates the cost of chronic LBP at $10 billion annually due to reduced productivity, while another study estimates a total of $100 billion annually due to healthcare costs, lost wages, and reduced productivity combined.2 Considering the many physiological, neurological, and psychological factors implicated in LBP, the diagnostic evaluation of patients is very challenging and requires complex clinical decision-making.3 Nevertheless, identifying the source of pain is of fundamental importance in determining a therapeutic approach for patients with LBP.3

LBP can derive from many different anatomical sources, such as muscle, bones, joints, nerve roots, fascial structures, intervertebral discs (IVDs), and organs within the abdominal cavity.3 In addition, symptoms may emerge from aberrant neurological pain processing causing neuropathic LBP.4-5 During the evaluation, the clinician must also consider the possible influence of psychological factors, such as stress, depression, and anxiety.6-7 In diagnosing LBP, clinical information is the key element as opposed to MRI. In fact, the American College of Radiology advises against MRI in the first 6 weeks (unless red flags appear) because imaging data is weakly related to symptoms. Overall, chronic LBP may arise from multiple pain generators simultaneously and therefore requires a multidisciplinary diagnosis with an accompanying multimodal treatment plan.8

The type of LBP depends on the pain generator. One example is radicular pain, which refers to pain due to ectopic discharges from an inflamed or lesioned dorsal root or its ganglion.3 Typically, pain radiates from the back and buttock into the leg in a dermatomal pattern. The most common pathophysiological cause of radicular pain is disc herniation, which results in inflammation at the nerve. Furthermore, radicular pain differs from radiculopathy in that the latter impairs conduction down a spinal nerve, leading to numbness and muscle weakness.3 Although the two often accompany each other, radicular pain can appear in the absence of radiculopathy and vice versa.3

Another example is facet joint syndrome, which accounts for up to 30% of chronic LBP cases.9 The lumbar zygapophyseal joints are formed from the inferior process of upper vertebra and the superior articular process of lower vertebra; furthermore, these joints have a large amount of free and encapsulated nerve ending, which activate nociceptive afferents.3 Patients with facet joint syndrome typically complain of LBP, sometimes with somatic referred pain in the legs and often radiating to the thigh or groin. Back pain tends to be off-center and of lower intensity than leg pain; pain also increases with hyperextension, rotation, lateral bending, and uphill walking.3 Lastly, patients may report back stiffness, especially during the morning.

Other pain generators associated with LBP include sacroiliac joint pain (SIJ), lumbar spinal stenosis (LSS), and discogenic pain. SIJ is well recognized as a source of pain in patients with chronic LBP. Pain associated with SIJ can arise from ligamentous or capsular tension, altered joint mechanics, extraneous compression or shear forces, hypermobility, and myofascial or kinetic chain dysfunction leading to inflammation.10 LSS is determined by progressive narrowing of the central spinal canal and lateral recesses, which consequently leads to compression of neurovascular structures.3 Most cases of LSS are degenerative and associated with structural changes in the spine due to aging. Lastly, disc degeneration is the pain generator in 39% of chronic LBP cases.3 In terms of the pathophysiology, disc degeneration is characterized by degradation of the nucleus pulposus matrix with accompanying radial and concentric fissures in the annulus fibrosus.3 Overall it is critical that clinicians perform a thorough evaluation to accurately diagnosis the cause of LBP and develop an effective multimodal treatment plan that rapidly alleviates symptoms.

References

1) Balagué F, Mannion AF, Pellisé F, et al.: Non-specific low back pain. Lancet. 2012;379(9814):482–91.

2) Montgomery W, Sato M, Nagasaka Y, Vietri J. The economic and humanistic costs of chronic lower back pain in Japan. Clinicoecon Outcomes Res. 2017;9:361–371.

3) Allegri M, Montella S, Salici F, et al. Mechanisms of low back pain: a guide for diagnosis and therapy. F1000Res. 2016;5: F1000 Faculty Rev-1530.

4) Smart KM, Blake C, Staines A, et al. : Mechanisms-based classifications of musculoskeletal pain: part 1 of 3: symptoms and signs of central sensitization in patients with low back (+/- leg) pain. Man Ther. 2012;17(4):336–44.

5) Garland EL: Pain processing in the human nervous system: a selective review of nociceptive and biobehavioral pathways. Prim Care. 2012;39(3):561–71.

6)  Besen E, Young AE, Shaw WS: Returning to work following low back pain: towards a model of individual psychosocial factors. J Occup Rehabil. 2015;25(1):25–37.

7) Deyo RA, Bryan M, Comstock BA, et al.: Trajectories of symptoms and function in older adults with low back disorders. Spine (Phila Pa 1976). 2015;40(17):1352–62.

8) Boden SD, Davis DO, Dina TS, et al.: Abnormal magnetic-resonance scans of the lumbar spine in asymptomatic subjects. A prospective investigation. J Bone Joint Surg Am. 1990;72(3):403–8.

9) van Kleef M, Vanelderen P, Cohen SP, et al.: 12. Pain originating from the lumbar facet joints. Pain Pract. 2010;10(5):459–69.

10)  Dreyfuss P, Dreyer SJ, Cole A, et al.: Sacroiliac joint pain. J Am Acad Orthop Surg. 2004;12(4):255–65.

Manipulation Under Anesthesia

Manipulation under anesthesia (MUA) was originally practiced by orthopedic and osteopathic physicians for the management of spinal pain since the 1930s. Today, the practice is currently acceptable for management of several other conditions including: arthrofibrosis, reduction of fractures, contractures and pain management of musculoskeletal conditions. This article will briefly discuss the indications, relevant physiology, risks, benefits, and steps of MUA for the management of several musculoskeletal conditions.

The practice of MUA requires an understanding of the effects of anesthesia on neuro-musculoskeletal innervation, signal transduction, and tissue manipulation. Systemic anesthesia will impair the protective innate tissue reflexes that exist in muscle tissue as well as attenuate the transduction of pain signals centrally. After administration of a sufficient dose of anesthesia to cause either full or conscious sedation, the practitioner can begin to engage in anatomical range of motion of the area of interest. This can also occur intra-operatively. Anesthesia will allow for the reduction of innate muscle stretch reflexes and signal transduction of pain.

Manipulation treatments can include progressive stretch, high-velocity thrust, local deep tissue injections as well as aiding in positioning for targeted injection therapy. Often a single treatment session is needed. Benefits such as range of motion improvement and pain reduction can be seen immediately. Risks associated with this procedure include those associated with anesthetic administration as well as those carried by specific manipulation treatments.

Certain indications for MUA include pain in a restricted joint that is unresponsive to conservative care. One example of this is Adhesive Capsulitis (commonly referred to as Frozen Shoulder). This is as omni-directional pain and range of motion reduction of the shoulder after injury, metabolic and endocrine insults, or prolonged subluxation after conferring local tissue structural changes. MUA can be trialed after the patient has tried other conservative and interventional measures. MUA can aid in reducing tissue fibrosis and improving range of motion with attention paid to patient comfort.

MUA can also be offered for the reduction of fractures. Long bone fractures often require manipulation of the fractured bone under anesthesia to optimal healing position before fixation. In some cases, manipulation of the broken limb into optimal placement followed by casting is sufficient alone. It is important to note that there is less evidence to support the use of MUA for acute and chronic axial pain conditions.

Contracture of an extremity can be seen after prolonged range of motion restriction of an affected extremity either from neurological or traumatic causes. Less commonly, it can be seen post arthroplasty. One cause of contracture is Heterotopic Ossification and this is seen after significant neurological or skin trauma. Findings will typically include range of motion restriction, pain with use, decreased outcomes with post-illness rehabilitation, and serum biomarker elevation of bone metabolic activity. The most common joints affected are the hip, shoulder, and elbow. MUA can allow for a more aggressive range of motion therapy, which will aid in breaking up contracted elements.

In conclusion, MUA is a long-standing treatment plan for the management of musculoskeletal pain conditions. It involves the use of anesthesia to reduce innate neuro-musculoskeletal reflexes as well as patient discomfort for the management of range of motion restriction, fracture, and positioning of limbs for interventional treatment. Risks associated with treatment include those associated with anesthesia as well as specific manipulations and interventions. It is essential to weigh the risks and benefits of treatment and pursue more conservative treatments if available.

References

1. American Chiropractic Association. Spinal manipulation policy statement. Updated 2003. Accessed October 3, 2019: http://www.acatoday.org/SearchResults?Search=Spinal+manipulation+policy+statement

2. American Association of Manipulation Under Anesthesia Providers. Guidelines for the practice and performance of manipulation under anesthesia. Feb 3, 2014. Chiropr Man Therap. 2014; 22: 7.

3. Antuna SA, Morrey BF, Adams RA, O’Driscoll SW. Ulnohumeral arthroplasty for primary degenerative

arthritis of the elbow: long-term outcome and complications. J Bone Joint Surg Am. 2002Dec: 84-A(12):2168-73.

4. Araghi A, Celli A, Adams R, Morrey B. The outcome of examination (manipulation) under anesthesia on the stiff elbow after surgical contracture release. Shoulder Elbow Surg. 2010 Mar;19(2):202-8.

5. Assendelft WJJ, Morton SC, Yu EI, Suttorp MJ, Shekelle PG. Spinal manipulative therapy for low-back pain. The Cochrane Database of Systematic Reviews 2005 Issue 4. In: The Cochrane Library, Issue 4, 2005.

6. Chao EK, Chen AC, Lee MS, Ueng SW. Surgical approaches for nonneurogenic elbow heterotopic ossification with ulnar neuropathy. J Trauma. 2002 Nov;53(5):928-33.

7. Charalambous CP, Morrey BF. Posttraumatic elbow stiffness. J Bone Joint Surg Am. 2012 Aug 1;94(15):1428-37.

8. Cremata E, Collins S, Clauson W, Solinger AB, Roberts ES. Manipulation under anesthesia: a report of four cases. J Manipulative Physiol Ther. 2005 Sep;28(7):526-33.

The Effects of Chiropractic Spinal Adjustments in a Case of Uveitis

Anterior uveitis refers to an inflammatory condition of the iris and ciliary body, while posterior uveitis refers to an inflammatory condition of the choroid.1 Both conditions cause blurred vision due to opacities in the intraocular fluid. In addition, lesions within the eye cause reduced vision and increased awareness of floaters, dark spots that drift across the field of vision.1 Children with uveitis may report pain, photophobia, lacrimation, blepharospasm, and disturbed vision – or, the patient may be asymptomatic. Several researchers report correlations between uveitis and other conditions, such as ankylosing spondylitis, sacroilitis, juvenile chronic arthritis, herpes simplex and connective tissue diseases.2 Other studies show a correlation between posterior uveitis and disorders of the central nervous system, such as toxoplasmosis. However, one third of patients with uveitis display no association with any other diseases.2,3

In a case study, a male child aged 5.75 years was diagnosed with anterior and posterior uveitis based on a thorough ophthalmological examination. Visual acuity was 20/100 in the right eye and 20/30 in the left eye; slit lamp examination showed evidence of anterior uveitis with 2+ cells and flare in each anterior chamber; and a broken synechia was identified in the right eye with mild changes of the lens consistent with inflammation.1 Ophthalmoscopic monitoring continued over a four month course of topical and systemic steroid therapy. However, no significant improvement was observed based on the Snellen eye chart and fundus examination. Therefore, steroid therapy was discontinued and chiropractic treatment was taken into consideration.1

During the chiropractic consultation, a thorough history was performed. The patient suffered from chronic bronchitis since infancy; at three years, the patient fell from the bed and lacerated his left eyelid; at five years, the patient fell from the bed again and reported leg and knee pain; the patient complained of intermittent neck and back pain and leg, knee, and ankle pain; and lastly the patient complained of pain in the proximal interphalangeal joints of all fingers.2 During spinal examination, the patient presented with a mild dextro-scoliosis in the thoracic spine and a mild levoscoliosis in the lumbar spine. Although the range of motion in the cervical spine was normal, pain at C3 to C5 was noted during neck extension.2 Furthermore, the patient reported pain at C7 during forward flexion, and pain in the area of the contralateral trapezius muscle during neck rotation.2  Lastly, static and motion palpation of the spine revealed segmental subluxations, muscle induration, fixation, and misalignments at several spinal levels.1 Therefore, a course of spinal adjustments was commenced.

Spinal adjustments were initially delivered at a frequency of three times per week and later reduced to two times per month after improvement in visual acuity was achieved. After the second visit for spinal adjustment, visual acuity was 20/80 in the right eye and 20/20 in the left eye. After the sixth visit, visual acuity was 20/50 in the right eye and 20/20 in the left eye. A year after chiropractic treatment, an ophthalmologist and optometrist verified improvement in visual acuity (20/30 for the right eye) based on Snellen chart tests.1

To understand the link between uveitis and spinal adjustment therapy, one must consider the neurological and internal anatomy of the eye. The superior cervical ganglion receives preganglionic fibers from the first thoracic nerve and supplies postganglionic fibers to the internal carotid and cavernous plexuses. In turn, the internal carotid and cavernous plexuses supply sympathetic fibers to the vasculature of the eye. Alteration of the sympathetic nerve supply may lead to tissue neovascularization and increase the possibility of rupture with trauma and histamine release.4 Therefore, correction of associated nerve irritation via spinal adjustment may reverse symptoms of uveitis.

References

1) Manuele, J and Fysh, P. “The Effects of Chiropractic Spinal Adjustments in a Case of Bilateral Anterior and Posterior Uveitis.” Journ of Clin Chiro Ped. 2004; 6:334-337.

2) Szanto E, Granfors K, Wretlind B. Acute anterior uveitis, arthritis and enteric antigens. Clin Rheumatol 1991; 4:395-400.

3) Linssen A, et al. “The lifetime cumulative incidence of acute anterior uveitis in a normal population and its relation to ankylosing spondylitis and histocompatibility antigen HLAB27.” Ophthal Vis Sci. 1991; 9:2568-78.

4) Oski, FA. Principles and Practice of Pediatrics, 2nd ed. Philadelphia; Lippincott 1994; 34:891.

Sciatica: Symptoms, Mechanisms, and Treatment

Sciatica is a debilitating condition in which patients experience pain or paresthesia along the path of the sciatic nerve in a dermatomal pattern. Up to 2 cm in diameter, the sciatic nerve is the largest in the body and – directly or indirectly – innervates the hamstrings, lower extremity adductors, calf muscles, anterior lower leg muscles, and intrinsic foot muscles.1-3 In the general population, the annual prevalence of disc related sciatica is 2.2%.1 In patients with low back pain, the annual prevalence is 5-10%.1 Risk factors include age, height, smoking, stress, strenuous activity, and exposure to whole body vibration (e.g. in a car).4 Epidemiologically, sciatica displays no gender predominance, peak incidence in the fourth decade, a genetic predisposition, and an occupational predisposition (e.g. in machine operators and truck drivers).4

Sciatica is primarily diagnosed by history taking and physical examination. Patients with sciatica commonly report unilateral pain in the lumbar spine, pain or burning sensations deep in the buttocks, and paresthesia.5 Less commonly, patients report ipsilateral leg weakness. Physical examination depends on neurological testing, such as the straight leg raising test. In the straight leg raising test, the patient lays in a relaxed, supine position while the examiner lifts the leg from the posterior, flexing at the hip joint and keeping the knee in full extension. Typically, pain experienced between 30 and 70 degrees of hip flexion indicates a lumbar disc herniation.4 Overall, the diagnosis of sciatica is justified if a patient reports radiating pain in one leg and demonstrates nerve root tension or neurological deficits based on a positive result on one or more neurological tests.4

Anatomically, the sciatic nerve is comprised of the L4 through S2 nerve roots, which merge at the pelvic cavity and exit posteriorly through the sciatic foramen.5 The sciatic nerve then travels inferior and anterior to the piriformis, and posterior to the gemellus superior, gemellus inferior, obturator internus, and quadratus femoris.5 Next, the sciatic nerve enters the posterior thigh, travels to the biceps femoris, and terminates at the knee in the popliteal folsa.5 Sciatica occurs when the nerve is pinched or compressed anywhere along the aforementioned pathway. In 90% of cases, sciatica is caused by a herniated disc with associated nerve root compression.4 However, sciatica is also caused by several other pathologies, including:

Muscle spasm

Nerve root impingement

Epidural abscess

Epidural hematoma

Tumor

Spinal tuberculosis

Piriformis syndrome

The prognosis for sciatica is quite favorable, with most cases resolving in 4 to 6 weeks with no long-term consequences. For example, a randomized trial involving non-steroidal anti-inflammatory drugs showed that 60% of patients recovered within three months and 70% within 12 months.6 That said, recovery is more prolonged in severe cases involving neurological deficits. Accordingly, some studies suggest that up to 30% of patients experience pain for a year or longer.6-7 Therefore, it is advised to seek treatment to avoid chronic and recurrent pain.

Chiropractic treatment for sciatica is non-invasive, non-surgical, and drug-free. The type of treatment depends on the cause of sciatica, but may include a combination of ice therapy, ultrasound, transcutaneous electrical nerve stimulation, and spinal adjustments. Ice therapy alleviates sciatic pain by reducing inflammation.8 Ultrasound therapy involves sound waves that penetrate deep into soft tissue, which increases circulation and reduces muscles spasms, cramping, swelling, stiffness, and sciatic pain.8 

In transcutaneous electrical nerve stimulation, a machine generates variable amounts of electrical current to reduce muscle spasms and alleviate pain.8  Spinal manipulation frees restricted movement of the spine by restoring misaligned vertebral bodies to their proper position in the spinal column; this alleviates inflammation, muscle spasms, and sciatic pain.8 Overall, sciatica is a debilitating condition that can significantly affect one’s quality of life. Patients displaying symptoms should seek chiropractic care to alleviate their pain and restore their quality of life.

References

1) Lagerbäck T, Fritzell P, Hägg O, Nordvall D, Lønne G, Solberg TK, Andersen MØ, Eiskjær S, Gehrchen M, Jacobs WC, van Hooff ML, Gerdhem P. Effectiveness of surgery for sciatica with disc herniation is not substantially affected by differences in surgical incidences among three countries: results from the Danish, Swedish and Norwegian spine registries. Eur Spine J. 2019 Nov;28(11):2562-2571.

2) Alrwaily M, Almutiri M, Schneider M. Assessment of variability in traction interventions for patients with low back pain: a systematic review. Chiropr Man Therap. 2018;26:35.

3) Hong X, Shi R, Wang YT, Liu L, Bao JP, Wu XT. Lumbar disc herniation treated by microendoscopic discectomy : Prognostic predictors of long-term postoperative outcome. Orthopade. 2018 Dec;47(12):993-1002.

4) Koes BW, van Tulder MW, Peul WC. Diagnosis and treatment of sciatica. BMJ. 2007;334(7607):1313–1317.

5) Delgado-López PD, Rodríguez-Salazar A, Martín-Alonso J, Martín-Velasco V. [Lumbar disc herniation: Natural history, role of physical examination, timing of surgery, treatment options and conflicts of interests]. Neurocirugia (Astur). 2017 May – Jun;28(3):124-134.

6) Weber H, Holme I, Amlie E. The natural course of acute sciatica with nerve root symptoms in a double blind placebo-controlled trial of evaluating the effect of piroxicam (NSAID). Spine 1993;18:1433-8.

7) Vroomen PCAJ, Krom MCTFM de, Slofstra PD, Knottnerus JA. Conservative treatment of sciatica: a systematic review. J Spinal Dis 2000;13:463-9.

8) Grassi R. Chiropractic Treatment of Sciatica. Remedy Health Media. Spine Universe. 2020.

Migraines: Presentation, Mechanisms, and Management

Migraines: Presentation, Mechanisms, and Management

Migraines remain an important public health issue that can significantly affect one’s daily activities and quality of life. The prevalence of migraines in the US adult population is quite high, affecting 15.3% of individuals. Relative to the general population, the prevalence is higher for those with disabilities (16.4%), aged 18-44 (17.9%), and on low income (19.9%). Additionally, the prevalence in women (20.7%) is much higher than in men (9.7%). Annually, migraines account for 3% of all visits to the emergency department, consistently among the top four or five leading causes.1

Symptomatically, migraines progress through four stages: prodrome, aura, attack, and post-drome. One to two days before a migraine –  i.e. prodrome – subtle changes warn of an upcoming attack, including constipation, mood changes, food cravings, neck stiffness, increased thirst, and frequent yawning. As a migraine progresses, individuals may experience auras, or reversible symptoms of the nervous system that begin gradually and last 20 to 60 minutes. Examples of auras include visual phenomena (e.g. bright spots, shapes, and flashes), vision loss, pins and needles in the arms and legs, facial numbness, difficulty speaking, hearing noises, and uncontrollable jerking movements. During an attack, which can last 4 to 72 hours if untreated, individuals may experience pain on one or both sides of the head, throbbing sensations, sensitivity to light and sound, nausea, and vomiting. After an attack – i.e. post-drome – individuals may feel drained and confused for up to a day.2

Over the past few decades, our understanding of the pathophysiology of migraines has improved considerably. Previously, the vascular theory was the leading explanation for migraines; however, a series of imaging studies demonstrated that vascular changes were neither necessary nor sufficient for attacks.3-4 From vascular theories, researchers moved to neuronal theories involving the peripheral and central nervous systems. Initially, researchers attempted to localize a single structure as the source of migraines; but it is now clear that migraines are a complex brain network disorder with a genetic basis that involves multiple cortical, subcortical, and brainstem regions.4-6

The trigeminovascular system is a key actor and its activation is thought to initiate the cascade of events resulting in migraines due to its direct connection with the diencephalic and brainstem nuclei.7-8  The literature also supports the involvement of the hypothalamus in migraines. For example,several studies demonstrate hypothalamic connections to the thalamus, trigeminovascular system, and brainstem nuclei, supporting the role of the hypothalamus in pain modulation in patients with migraines.9-11 The involvement of the hypothalamus may explain some of the early symptoms of migraines, such as food cravings, mood swings, and yawning. Additionally, the thalamus may play a role in migraines. The thalamus is a nociceptive relay station that conveys information from the dura mater and cutaneous areas to second-order trigeminovascular areas. Several studies report structural and functional thalamic alterations in patients with migraines.12-13 Furthermore, changes in the structure and function of key cortical areas were demonstrated in migraineurs, such as the insular, somatosensory, prefrontal, and cingulate cortex.14 Lastly, a variety of factors may trigger migraines, including hormonal changes in women, alcohol, coffee, stress, sensory stimuli, sleep changes, weather changes, medication, and processed foods.

Chiropractic spinal manipulative therapy (CSMT) is supported by numerous studies as an effective treatment option for migraines. In a randomized controlled trial of 172 patients, Tuchin et al demonstrated that patients receiving CSMT reported a significant improvement in migraine frequency, duration, disability, and medication use. A more recent study by Chaibi et al involved a 52 year old woman suffering from migraines once per month, with pain scored as an 8 out of 10. After CSMT treatment, the patient reported a complete elimination of migraines. At a follow up 6 months later, the patient did not report a single migraine episode during the intervening period.16 Overall, evidence suggests that CSMT can alleviate pain from migraines, making chiropractic care a viable option for individuals suffering from migraines.

References

1) Burch R, Rizzoli P, Loder E. The prevalence and impact of migraine and severe headache in the United States: figures and trends from government health studies. Headache: The Journal of Head and Face Pain. 2018;58(4):496–505.

2) Mayo Clinic Staff. Migraine. Mayo Foundation for Medical Education and Research. Nov. 2019.

3) Amin FM, Asghar MS, Hougaard A, Hansen AE, Larsen VA, de Koning PJ, Larsson HB, Olesen J, Ashina M. Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study. Lancet Neurol. 2013;12:454–461.

4) Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine—a disorder of sensory processing. Physiol Rev. 2017;97(2):553–622.

5) Charles A. Migraine: a brain state. Curr Opin Neurol. 2013;26:235–239.

6)  Ferrari MD, Klever RR, Terwindt GM, Ayata C, van den Maagdenberg AM. Migraine pathophysiology: lessons from mouse models and human genetics. Lancet Neurol. 2015;14:65–80.

7) Goadsby PJ, Charbit AR, Andreou AP, Akerman S, Holland PR. Neurobiology of migraine. Neuroscience. 2009;161:327–341.

8) Akerman S, Holland PR, Goadsby PJ. Diencephalic and brainstem mechanisms in migraine. Nat Rev Neurosci. 2011;12:570–584.

9)  Kagan R, Kainz V, Burstein R, Noseda R. Hypothalamic and basal ganglia projections to the posterior thalamus: possible role in modulation of migraine headache and photophobia. Neuroscience. 2013;248:359–368.

10) Abdallah K, Artola A, Monconduit L, Dallel R, Luccarini P. Bilateral descending hypothalamic projections to the spinal trigeminal nucleus caudalis in rats. PLoS One. 2013;8:e73022.

11) Robert C, Bourgeais L, Arreto CD, Condes-Lara M, Noseda R, Jay T, Villanueva L. Paraventricular hypothalamic regulation of trigeminovascular mechanisms involved in headaches. J Neurosci. 2013;33:8827–8840.

12) Magon S, May A, Stankewitz A, Goadsby PJ, Tso AR, Ashina M, Amin FM, Seifert CL, Chakravarty MM, Muller J, Sprenger T. Morphological abnormalities of thalamic subnuclei in migraine: a multicenter MRI study at 3 tesla. J Neurosci. 2015;35:13800–13806.

13) Hodkinson DJ, Wilcox SL, Veggeberg R, Noseda R, Burstein R, Borsook D, Becerra L. Increased amplitude of thalamocortical low-frequency oscillations in patients with migraine. J Neurosci. 2016;36:8026–8036.

14) Sprenger T, Borsook D. Migraine changes the brain: neuroimaging makes its mark. Curr Opin Neurol. 2012;25:252–262.

15) Tuchin P, Pollard H, Bonello R. A randomized controlled trial of chiropractic spinal manipulative therapy for migrain. J Manip Physio Therap. 2000;23:91-95.

16) Chaibi A, Tuchin PJ. Chiropractic spinal manipulative treatment of migraine headache of 40-year duration using Gonstead method: a case study. J Chiropr Med. 2011;10(3):189–193.