Sleep Deprivation Aggravates Median Nerve Injury-Induced Neuropathic Pain and Enhances Microglial Activation by Suppressing Melatonin Secretion

Huang, Chun-Ta; Chiang, Rayleigh Ping-Ying; Chen, Chih-Li; Tsai, Yi-Ju

doi:10.5665/sleep.4002

Cited by 65 publications

(44 citation statements)

References 71 publications

(79 reference statements)

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“…They concluded that NP-like stimuli can suppress γ-aminobutyric acid (GABAergic) transmission with increased GABA transporters located on activated astrocytes in the cingulate cortex related to sleep disturbance. In another experimental study, it was shown that sleep deprivation makes rats more vulnerable to nerve injury-induced NP probably because of associated lower melatonin levels [20]. Although these observations, at least in part, might explain the sleep disturbances in patients with NP, there appears to be a need for clarifying this association.…”

Section: Discussionmentioning

confidence: 96%

Does Neuropathic Pain Affect the Quality of Sleep?

Melikoğlu

Çelik

2017

Eurasian J Med

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Objective: We aimed to evaluate the quality of sleep (QoS) in patients with neuropathic pain (NP) and to investigate the association between possible QoS impairment and NP characteristics. Materials and Methods:Patients with NP and controls were examined. Age, sex, NP duration, NP cause (central, peripheral, or mixed), and pain intensity (with a Likert-type scale and visual analog scale) were recorded. NP was screened with Douleur Neuropathique 4 questions (DN4), and QoS was evaluated using the Pittsburg Sleep Quality Index (PSQI). Mann-Whitney U test and regression analysis were performed to evaluate the data.Results: Seventy patients with NP and 30 age-and sex-matched controls were included. The mean age of the patients and controls were 45.04±10.21 years and 39.00±19.23 years, respectively. Significantly higher scores of sleep latency (p=0.002), sleep duration (p=0.003), sleep efficiency (p=0.002), sleep disturbance (p<0.000), daytime dysfunction (p=0.04), and PSQI total were observed in patients with NP than in controls (p<0.000). In addition, 80% of patients with NP and 37 % of controls were classified as having poor QoS (p<0.000). Female sex, pain intensity, and NP duration were found to be factors related to having poor QoS in patients with NP (p=0.026, p=0.006, and p<0.000, respectively). Conclusion:In our study, 80% of patients with NP had poor QoS regardless of the NP cause. Female sex, pain severity, and NP duration were found to be factors correlated with poor QoS. Treatment strategies that target not only NP itself but also better QoS may contribute to the overall success of management.Keywords: Neuropathic pain, quality of sleep, pain ÖZ Amaç: Bu çalışmanın amacı nöropatik ağrı (NA) tanısı alan hastalarda uyku kalitesini değerlendirmek uyku kalitesindeki bozulma ile NA'nın özellikleri arasındaki olası ilişkileri incelemekti.Gereç ve Yöntem: Bu çalışmaya NA'lı hastalar ve sağlıklı kontroller dahil edildi. Yaş, cinsiyet, NA süresi, NA nedeni (santral, periferik veya mikst) ve ağrı yoğunluğu (görsel analof skala ve Likert tipi skala ile) kaydedildi. NA (Douleur Neuropathique4 (DN4) anketi ile, uyku kalitesi ise Pittsburg uyku kalitesi indeksi (PUKİ) ile değerlendirildi. Mann-Whitney U testi ve regresyon analizi uygulandı. Bulgular: Bu çalışmaya NA'lı 70 hasta (54 kadın, 16 erkek) ile yaş ve cinsiyet olarak benzer 30 kontrol dahil edildi. Hastaların ve kontrollerin ortalama yaşları sırasıyla 45,04±10,21 ve 39,00±19,23 yıl idi. Hastalarda semptom süresi 24,8±18,2 olarak kaydedildi. NA'lı hastalarda sağlıklılara göre PUKİ bileşenlerinden uykuya geç geçiş (p=0,002), uyku süresi (p=0,003), uyku etkinliği (p=0,002), uyku disturbansı (p<0,000), gündüz disfonksiyonu (p=0,04) ve total PUKİ skoru (p<0,000) anlamlı şekilde daha yüksek tespit edildi. Ayrıca NA'lı hastaların %80'inin ve kontrollerin %37' sinin kötü uyku kalitesine sahip oldukları kaydedildi (p<,000). NA'lı hastalarda kadın cinsiyet, ağrı yoğunluğu ve semptom süresi kötü uyku kalitesi ile ilişkili faktörler olarak tespit edildi (p=0,026, p=...

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Section: Discussionmentioning

confidence: 96%

Does Neuropathic Pain Affect the Quality of Sleep?

Melikoğlu

Çelik

2017

Eurasian J Med

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“…injection of sodium pentobarbital (30–40 mg/kg) and the right median nerve was separated from the surrounding tissues at the elbow level and between two heads of the pronator teres muscle under a dissecting microscope. Four loose ligatures were made to tie around the nerve using a 4.0 chromic gut suture (Chen et al, ; Day, Lue, Sun, Shieh, & Wen, ; Huang, Chiang, Chen, & Tsai, ; Tsai et al, ; Tsai, Huang, Lin, & Yeh, ), and then the incision was sutured. For the sham surgeries, the median nerve was exposed in the same area of the right forelimb without ligation.…”

Section: Methodsmentioning

confidence: 99%

Erythropoietin reduces nerve demyelination, neuropathic pain behavior and microglial MAPKs activation through erythropoietin receptors on Schwann cells in a rat model of peripheral neuropathy

Huang

Chen

Lin

et al. 2018

Glia

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Neuroprotective effects of erythropoietin (EPO) on peripheral nerve injury remain uncertain. This study investigated the efficacy of EPO in attenuating median nerve chronic constriction injury (CCI)‐induced neuropathy. Animals received an intraneural injection of EPO at doses of 1,000, 3,000, or 5,000 units/kg 15 min before median nerve CCI. Afterwards, the behavioral and electrophysiological tests were conducted. Immunohistochemistry and immunoblotting were used for qualitative and quantitative analysis of microglial and mitogen‐activated protein kinases (MAPKs), including p38, JNK, and ERK, activation. Enzyme‐linked immunosorbent assay and microdialysis were applied to measure pro‐inflammatory cytokine and glutamate responses, respectively. EPO pre‐treatment dose‐dependently ameliorated neuropathic pain behavior, decreased microglial and MAPKs activation, and diminished the release of pro‐inflammatory cytokines and glutamate in the ipsilateral cuneate nucleus after CCI. Moreover, EPO pre‐treatment preserved myelination of the injured median nerve on morphological investigation and suppressed injury‐induced discharges. We also observed that EPO receptor (EPOR) expression was up‐regulated in the injured nerve after CCI. Double immunofluorescence showed that EPOR was localized to Schwann cells. Furthermore, siRNA‐mediated knockdown of EPOR expression eliminated the therapeutic effects of EPO on attenuating the microglial and MAPKs activation, pro‐inflammatory cytokine responses, injury discharges, and neuropathic pain behavior in CCI rats. In conclusion, binding of EPO to its receptors on Schwann cells maintains myelin integrity and blocks ectopic discharges in the injured median nerve, that in the end contribute to attenuation of neuropathic pain via reducing glutamate release from primary afferents and inhibiting activation of microglial MAPKs and production of pro‐inflammatory cytokines.

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“…As concerns neuropathy, we use a similar approach as in Section 3.3 and consider both (a) an inhibitory effect of the A fibers to the C fibers represented by amplitude modulation of the C fibers by the Aβ fibers as given in Equation (5), and (b) circadian rhythm in the C and Aβ fibers. In addition, we use the amended model to investigate the hypothesis that under neuropathy, time spent awake causes increased excitatory input from the mid-brain to the dorsal horn circuit [14]. Thus, Fig.…”

Section: Model Validationmentioning

confidence: 99%

“…We also aim to include a mechanism for the effect of the homeostatic sleep drive on this top-down inhibition. As shown in [14] and [32], the build up of the homeostatic sleep drive is reflected in the daily rhythm of the pro-inflammatory cytokines, whose increased levels are associated with an increased firing rate of the WDR projection neurons. We model this by assuming that the connection from the mid-brain to the dorsal horn circuit is a function of the time spent awake, or the build-up of the homeostatic sleep drive.…”

Section: Introductionmentioning

confidence: 99%

Investigating circadian rhythmicity in pain sensitivity using a neural circuit model for spinal cord processing of pain

Crodelle

Piltz

Booth

et al. 2017

Preprint

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Primary processing of painful stimulation occurs in the dorsal horn of the spinal cord. In this article, we introduce mathematical models of the neural circuitry in the dorsal horn responsible for processing nerve fiber inputs from noxious stimulation of peripheral tissues and generating the resultant pain signal. The differential equation models describe the average firing rates of excitatory and inhibitory interneuron populations, as well as the wide dynamic range (WDR) neurons whose output correlates with the pain signal. The temporal profile of inputs on the different afferent nerve fibers that signal noxious and innocuous stimulation and the excitability properties of the included neuronal populations are constrained by experimental results. We consider models for the spinal cord circuit in isolation and when topdown inputs from higher brain areas that modulate pain processing are included. We validate the models by replicating experimentally observed phenomena of A fiber inhibition of pain and wind-up. We then use the models to investigate mechanisms for the observed phase shift in circadian rhythmicity of pain that occurs with neuropathic pain conditions. Our results suggest that changes in neuropathic pain

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Sleep Deprivation Aggravates Median Nerve Injury-Induced Neuropathic Pain and Enhances Microglial Activation by Suppressing Melatonin Secretion

Cited by 65 publications

References 71 publications

Does Neuropathic Pain Affect the Quality of Sleep?

Does Neuropathic Pain Affect the Quality of Sleep?

Erythropoietin reduces nerve demyelination, neuropathic pain behavior and microglial MAPKs activation through erythropoietin receptors on Schwann cells in a rat model of peripheral neuropathy

Investigating circadian rhythmicity in pain sensitivity using a neural circuit model for spinal cord processing of pain

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