Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.

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Central sensitization: implications for the diagnosis and treatment of pain.

A set of related medical disorders that lack a proper classification system and diagnostic criteria is like a society without laws. The result is incoherence at best, chaos at worst. For this reason, the International Classification of Headache Disorders (ICHD) is arguably the single most important breakthrough in headache medicine over the last 50 years. The ICHD identifies and categorizes more than a hundred different kinds of headache in a logical, hierarchal system. Even more important, it has provided explicit diagnostic criteria for all of the headache disorders listed. The ICHD quickly became universally accepted, and criticism of the classification has been minor relative to that directed at other disease classification systems. Over the 20 years following publication of the first edition of the ICHD, headache research has rapidly accelerated despite sparse allocation of resources to that effort. In summary, the ICHD has attained widespread acceptance at the international level and has substantially facilitated both clinical research and clinical care in the field of headache medicine.

International Classification of Headache Disorders

ContextSpontaneous intracranial hypotension is caused by spontaneous spinal cerebrospinal fluid (CSF) leaks and is known for causing orthostatic headaches. It is an important cause of new headaches in young and middle-aged individuals, but initial misdiagnosis is common.ObjectiveTo summarize existing evidence regarding the epidemiology, pathophysiology, diagnosis, and management of spontaneous spinal CSF leaks and intracranial hypotension.Evidence AcquisitionMEDLINE (1966-2005) and OLDMEDLINE (1950-1965) were searched using the terms intracranial hypotension, CSF leak, low pressure headache, and CSF hypovolemia. Reference lists of these articles and ongoing investigations in this area were used as well.Evidence SynthesisSpontaneous intracranial hypotension is caused by single or multiple spinal CSF leaks. The incidence has been estimated at 5 per 100 000 per year, with a peak around age 40 years. Women are affected more commonly than men. Mechanical factors combine with an underlying connective tissue disorder to cause the CSF leaks. An orthostatic headache is the prototypical manifestation but other headache patterns occur as well, and associated symptoms are common. Typical magnetic resonance imaging findings include subdural fluid collections, enhancement of the pachymeninges, engorgement of venous structures, pituitary hyperemia, and sagging of the brain (mnemonic: SEEPS). Myelography is the study of choice to identify the spinal CSF leak. Treatments include bed rest, epidural blood patching, percutaneous placement of fibrin sealant, and surgical CSF leak repair, but outcomes have been poorly studied and no management strategies have been studied in properly controlled randomized trials.ConclusionsSpontaneous intracranial hypotension is not rare but it remains underdiagnosed. The spectrum of clinical and radiographic manifestations is varied, with diagnosis largely based on clinical suspicion, cranial magnetic resonance imaging, and myelography. Numerous treatment options are available, but much remains to be learned about this disorder.

https://jamanetwork.com/journals/jama/articlepdf/202849/JCR60004.pdf

Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension

Two-pore domain K+ (K2P) channels give rise to leak (also called background) K+ currents. The well-known role of background K+ currents is to stabilize the negative resting membrane potential and c...

/pdf/molecular-background-of-leak-k-currents-two-pore-domain-3xd1km54it.pdf

Molecular Background of Leak K+ Currents: Two-Pore Domain Potassium Channels

TMS and drugs

To investigate neglect, extinction, and body-perception in patients suffering from complex regional pain syndrome (CRPS). So-called 'neglect-like' symptoms have been reported in CRPS, however no studies have yet analyzed this phenomenon which might substantiate the theory of the central nervous system involvement in the pathophysiology of CRPS. A total of 114 patients with CRPS of the upper limb underwent bedside neurological examination. 'Neglect-like' symptoms were determined by asking all patients what kind of feeling they had toward the affected hand (feeling of foreignness). Hemispatial neglect was tested with the line bisection task in 29 patients and sensory extinction to simultaneous stimulation in 40 patients. The ability to identify fingers after tactile stimulation was tested in 73 patients. Independently of the affected side and disease duration, 54.4% of the patients reported that their hand felt 'foreign' or 'strange'. The ability to identify fingers was impaired in 48% on the affected hand and in 6.5% on the unaffected hand ( X(2) = 33.52, df = 1, p < 0.0001). These findings were related to pain intensity, illness duration and the extent of sensory deficits. No typical abnormalities indicating neglect were found in the line bisection test. Sensory extinction was normal in all patients. A large proportion of CRPS patients have disturbances of the self-perception of the hand, indicating an alteration of higher central nervous system processing. There are no indicators that classic neglect or extinction contribute to these findings. Physical therapy of such patients should take this observation into consideration.

Impaired self-perception of the hand in complex regional pain syndrome (CRPS)

BACKGROUND AND PURPOSE: Postural headache most often occurs after lumbar puncture as post–lumbar puncture headache (PLPH) or, rarely, spontaneously as spontaneous intracranial hypotension headache (SIHH). In this prospective study, we used spinal MR imaging to determine the findings that would assist in the diagnosis of PLPH and SIHH and that would further our pathophysiological understanding of postural headache. METHODS: The study group consisted of 15 healthy volunteers and 20 patients with postural headache: nine with SIHH and 11 with PLPH. The craniocervical junction and the cervical spine were studied using T2-weighted fast spin-echo and T1-weighted spin-echo sequences in the axial and sagittal planes. Follow-up studies were performed in 13 patients. RESULTS: Dilatation of the anterior internal vertebral venous plexus was the most constant finding, present in 17 (85%) of 20 patients with postural headache. Spinal hygromas, whose location as subdural or epidural could not be exactly determined, were present in 14 patients (70%). A focal fluid collection was detected in the retrospinal region at the C1–C2 level in six patients with SIHH and in four patients with PLPH (50%). Tonsillar descent was detected in only one patient, and subtentorial hygroma in five patients. No abnormalities were found in the volunteers. CONCLUSION: The MR signs of dilatation of the venous plexus, presence of spinal hygromas, and presence of retrospinal fluid collections can help to establish the diagnosis of intracranial hypotension. They are probably the result of decreased CSF volume, with the retrospinal fluid collections being a transudate from the venous plexus rather than frank extravasation. Resolution of these signs parallels resolution of the headache.

http://www.ajnr.org/content/ajnr/22/7/1239.full.pdf

Cervical MR Imaging in Postural Headache: MR Signs and Pathophysiological Implications

Objective.—To investigate the incidence and characteristics of seizure-associated headaches and the modalities of treatment.



Background.—Systematic investigations of the characteristics of seizure-associated headaches are rare. Although data in the literature on the incidence of postictal headaches range between 37% and 51%, experiences with their treatment are limited and pathophysiological concepts do not exist.



Methods.—One hundred ten epileptic outpatients from an epilepsy referral center participated in a semi-standardized interview about headaches associated with epileptic seizures. The characteristics of these patients and of 15 additionally recruited patients with known postictal headaches were analyzed.



Results.—The incidence of seizure-associated headaches was 43% (n = 47). Forty-three patients had exclusively postictal headaches. One patient had exclusively preictal headaches. Three patients had both pre- and postictal headaches. The duration of postictal headaches was longer than 4 hours in 62.5% of the patients. In the majority of patients, postictal headaches occurred in more than 50% of the seizures. Postictal headaches were treated by self-medication in 19 patients (30%). No patient treated headaches according to a medical prescription. In 11 patients, postictal migraine was untreated. Postictal headaches were associated with focal seizures in 23 patients and/or with generalized seizures in 54 patients. According to the headache classification of the International Headache Society, headaches were classified as migraine-type in 34% of patients and as tension-type headache in 34% of patients. Headaches could not be classified in 21% of patients. Patients with and without postictal headaches did not differ as to localization of the epileptogenic zone or to the number of prescribed antiepileptic drugs. There was no relationship between the localization of the epileptogenic focus, localization of the headache, or the headache classification.



Conclusions.—Headaches associated with partial and generalized seizures are frequent and undertreated. Treatment should consider both the headache syndrome and the general guidelines for treating primary headaches. The pathophysiology of seizure-associated headaches cannot be explained by the epileptic syndrome.

Headache Associated with Epileptic Seizures: Epidemiology and Clinical Characteristics

TMS motor cortical brain mapping in patients with complex regional pain syndrome type I.

Background: Sensory abnormalities are a key feature of Complex Regional Pain Syndrome (CRPS). In order to characterise these changes in patients suffering from acute or chronic CRPS I, we used Quantitative Sensory Testing (QST) in comparison to an age and gender matched control group. Methods: 61 patients presenting with CRPS I of the upper extremity and 56 healthy subjects were prospectively assessed using QST. The patients’ warm and cold detection thresholds (WDT; CDT), the heat and cold pain thresholds (HPT; CPT) and the occurrence of paradoxical heat sensation (PHS) were observed. Results: In acute CRPS I, patients showed warm and cold hyperalgesia, indicated by significant changes in HPT and CPT. WDT and CDT were significantly increased as well, indicating warm and cold hypoaesthesia. In chronic CRPS, thermal hyperalgesia declined, but CDT as well as WDT further deteriorated. Solely patients with acute CRPS displayed PHS. To a minor degree, all QST changes were also present on the contralateral limb. Conclusions: We propose three pathomechanisms of CRPS I, which follow a distinct time course: Thermal hyperalgesia, observed in acute CRPS, indicates an ongoing aseptic peripheral inflammation. Thermal hypoaesthesia, as detected in acute and chronic CRPS, signals a degeneration of A-delta and C-fibres, which further deteriorates in chronic CRPS. PHS in acute CRPS I indicates that both inflammation and degeneration are present, whilst in chronic CRPS I, the pathomechanism of degeneration dominates, signalled by the absence of PHS. The contralateral changes observed strongly suggest the involvement of the central nervous system.

https://rsds.org/wp-content/uploads/2015/02/Huge_Lauchart_Forderreuther_etal.pdf

Stefanie Förderreuther

Papers

Impaired self-perception of the hand in complex regional pain syndrome (CRPS)

Cervical MR Imaging in Postural Headache: MR Signs and Pathophysiological Implications

Headache Associated with Epileptic Seizures: Epidemiology and Clinical Characteristics

TMS motor cortical brain mapping in patients with complex regional pain syndrome type I.

Interaction of Hyperalgesia and Sensory Loss in Complex Regional Pain Syndrome Type I (CRPS I)