Familial insensitivity to pain (HSAN V) and a mutation in the <i>NGFB</i> gene. A neurophysiological and pathological study

Minde, Jan; Toolanen, Göran; Andersson, T.; Nennesmo, Inger; Remahl, Ingela Nilsson; Svensson, Olle; Solders, Göran

doi:10.1002/mus.20172

Cited by 76 publications

(81 citation statements)

References 31 publications

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“…Crucially, the stroking speeds most effective in eliciting CT activation correlate significantly with the highest pleasantness ratings . CT activation may even be necessary for a typical subjective experience of a caress: patients carrying a rare mutation resulting in reduced C-afferent density (Minde et al, 2004) perceive stroking as generally less pleasant compared with controls, showing a significantly flatter response profile across velocities (Morrison et al, 2011). Here, our choice of 3 versus 30 cm/s stroking for CT-optimal and -nonoptimal stimuli, respectively, was motivated by Löken et al's (2009) recordings from single afferent nerves in the forearms of awake human volunteers.…”

Section: Affective Touch and Ct Afferent Pathwaymentioning

confidence: 99%

Vicarious Responses to Social Touch in Posterior Insular Cortex Are Tuned to Pleasant Caressing Speeds

Morrison

Björnsdotter²,

Olausson³

2011

Journal of Neuroscience

251

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Background. Affective touch carries strong significance for social mammals, including humans. Gentle, dynamic touch of a kind that occurs during social interactions is preferentially encoded by a distinct neural pathway involving tactile C (CT) afferents, a type of unmyelinated afferent nerve found exclusively in hairy skin. CT afferents increase firing when the skin is stroked at a pleasant, caress-like speed of ϳ3 cm/s, and their discharge frequency correlates with the subjective hedonic experience of the caress. In humans, the posterior insula is a cortical target for CT afferents. Since the potential social relevance of affective touch extends to the touch interactions of others, we postulated that information from CT afferents in posterior insular cortex provides a basis for encoding observed caresses. Results. In two experiments, we exploited CT afferents' functionally unique tuning curve for stroking speed, demonstrating that a speed optimal for eliciting CT discharge (3 cm/s) also gives rise to higher BOLD responses in posterior insula than a nonoptimal speed (30 cm/s). When participants viewed videos of others' arms being stroked at CT-optimal versus -nonoptimal speeds, the posterior insula showed a similar response as to directly felt touch. Further, this region's response was specific for social interactions, showing no CT-related modulation for nonsocial dynamic-touch videos. Conclusions. These findings provide direct evidence for a functional relationship between CT signaling and processing in posterior insular cortex. Such selective tuning for CT-optimal signals in insula may allow recognition of the hedonic relevance of a merely observed caress.

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Section: Affective Touch and Ct Afferent Pathwaymentioning

confidence: 99%

Vicarious Responses to Social Touch in Posterior Insular Cortex Are Tuned to Pleasant Caressing Speeds

Morrison

Björnsdotter²,

Olausson³

2011

Journal of Neuroscience

251

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“…Although not suffering from painless fractures, they can manifest Charcot arthropathies at single or multiple joints, particularly in the lower extremities. Cognitive functions and basic reflexes are normal in carriers (Einarsdottir et al 2004;Minde et al 2004Minde et al , 2006Minde et al , 2009. A list of the most relevant clinical features of R221W carriers is provided in Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…Despite its rarity, the R221W mutation offers vital clinical and preclinical insight for pain syndromes by revealing relationships between small-fiber density and pain perception. The R221W mutation (Capsoni et al 2011;Einarsdottir et al 2004) selectively affects the density of thindiameter sensory afferents (Crowley et al 1994;Larsson et al 2009;Minde et al 2004) with severe loss of unmyelinated C-fibers and comparatively moderate loss of thinly myelinated A␦-fibers (Crowley et al 1994;Larsson et al 2009;Minde et al , 2006. It does not affect large myelinated A␤-fibers , which are typically negative for the primary NGF receptor TrkA in the cell bodies (Patapoutian and Reichardt 2001).…”

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confidence: 99%

“…This noninvasive method has been applied to quantify C-fiber loss in neuropathy secondary to diabetes and other etiologies (Einarsdottir et al 2004;Minde et al 2004Minde et al , 2006Minde et al , 2009Quattrini et al 2007;Tavakoli et al 2009Tavakoli et al , 2010Tavakoli et al , 2012. To further investigate the contribution of C-fiber density to clinical pain assessment scores and subjective pain evaluation, we also administered the Neuropathy Disability Score (NDS; Young et al 1993) and the Situational Pain Questionnaire (SPQ; Clark and Yang 1983).…”

mentioning

confidence: 99%

“…These clinical sequelae in homozygotes follow an autosomal recessive heritability pattern. Based on this clinical presentation of painless fractures without anhidrosis or mental retardation, these patients have been classified as having hereditary somatosensory and autonomic neuropathy type V (HSAN-V; Minde 2006;Minde et al 2004). Yet, of the 63 currently identified heterozygous carriers, most do not present with pain-or inflammation-related deficits and have been identified only through pedigree and genetic screening.…”

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confidence: 99%

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Rare human nerve growth factor-β mutation reveals relationship between C-afferent density and acute pain evaluation

Perini

Tavakoli

Marshall

et al. 2016

Journal of Neurophysiology

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Perini I, Tavakoli M, Marshall A, Minde J, Morrison I. Rare human nerve growth factor-␤ mutation reveals relationship between C-afferent density and acute pain evaluation. J Neurophysiol 16: 425-430, 2016. First published May 4, 2016 doi:10.1152/jn.00667.2015The rare nerve growth factor-␤ (NGFB) mutation R221W causes a selective loss of thinly myelinated fibers and especially unmyelinated C-fibers. Carriers of this mutation show altered pain sensation. A subset presents with arthropathic symptoms, with the homozygous most severely affected. The aim of the present study was to investigate the relationship between peripheral afferent loss and pain evaluation by performing a quantification of small-fiber density in the cornea of the carriers, relating density to pain evaluation measures. In vivo corneal confocal microscopy (CCM) was used to quantify C-fiber loss in the cornea of 19 R221W mutation carriers (3 homozygous) and 19 age-matched healthy control subjects. Pain evaluation data via the Situational Pain Questionnaire (SPQ) and the severity of neuropathy based on the Neuropathy Disability Score (NDS) were assessed. Homozygotes, heterozygotes, and control groups differed significantly in corneal C-nerve fiber density, with the homozygotes showing a significant afferent reduction. Importantly, peripheral C-fiber loss correlated negatively with pain evaluation, as revealed by SPQ scores. This study is the first to investigate the contribution of small-fiber density to the perceptual evaluation of pain. It demonstrates that the lower the peripheral small-fiber density, the lower the degree of reported pain intensity, indicating a functional relationship between small-fiber density and higher level pain experience.nerve growth factor-␤ gene mutation; corneal confocal microscopy; pain evaluation; Situational Pain Questionnaire; C-fiber NEW & NOTEWORTHY

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Epidemiology of hereditary sensory and autonomic neuropathy type IV and V in Japan

Haga

Kubota

Miwa

2013

American J of Med Genetics Pt A

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Hereditary sensory and autonomic neuropathy (HASN) refers to a group of rare congenital disorders characterized by loss of pain sensation and other sensory or autonomic abnormalities. Among them, a relatively large proportion of patients with HSAN type IV, which is accompanied by anhidrosis and intellectual disability, are reported from Israel and Japan. HSAN type V, with normal sweating and mental development, is rarely reported in Japan. In 2009, we founded a research group for congenital insensitivity to pain and performed the first epidemiological survey of HSAN types IV and V in Japan. Questionnaires were sent to a total of 3,488 certified training institutions of five nationwide medical societies comprising pediatricians, neurologists, orthopedic surgeons, and dentists. Answers were obtained from 1,610 institutions, and 192 HSAN patients (152 with type IV and 28 with type V) were reported from 105 institutions. After excluding duplicated patients, we identified a total of 62 current, 36 past, and five deceased patients for HSAN-IV, and a total of 14 current, 13 past, and 0 deceased patients for HSAN-V. Using these figures, we estimated that the number of Japanese patients with HSAN types IV and V as 130-210 and 30-60 patients, respectively. We identified no gender differences, and patients with a family history of the disorder were limited to affected siblings in both conditions. Most patients with HSAN-IV were 5-40 years of age, whereas half of the patients with HSAN-V were 40 years or older.

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Familial insensitivity to pain (HSAN V) and a mutation in the NGFB gene. A neurophysiological and pathological study

Cited by 76 publications

References 31 publications

Vicarious Responses to Social Touch in Posterior Insular Cortex Are Tuned to Pleasant Caressing Speeds

Vicarious Responses to Social Touch in Posterior Insular Cortex Are Tuned to Pleasant Caressing Speeds

Rare human nerve growth factor-β mutation reveals relationship between C-afferent density and acute pain evaluation

Epidemiology of hereditary sensory and autonomic neuropathy type IV and V in Japan

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