Neuropathic pain treatment: still a challenge

Nascimento, Osvaldo J. M.; Pessôa, Bruno Lima; Orsini, Marco; Ribeiro, Pedro; Davidovich, Eduardo; Pupe, Camila; Filho, Pedro Moreira; Dornas, Ricardo; Masiero, Lucas; Bittencourt, Juliana; Bastos, Victor Hugo

doi:10.4081/ni.2016.6322

Cited by 16 publications

(14 citation statements)

References 27 publications

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“…According to statistics, the prevalence of NP is 5–7%, and millions of patients suffer from NP globally [ 1 ]. Long-term pain not only affects sleep quality but causes depression and mental disorder, and even suicidal tendencies, and thus severely influences quality of life [ 2 ]. However, the specific mechanism of NP is unclear, and the treatment of NP remains a thorny problem.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen-Rich Saline Activated Autophagy via HIF-1α Pathways in Neuropathic Pain Model

Wang

Huo

Chen

et al. 2018

BioMed Research International

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Background Neuropathic pain is a chronic and intractable pain, with very few effective analgesics. It involves an impaired cell autophagy process. Hydrogen-rich saline (HRS) reportedly reduces allodynia and hyperalgesia in a neuropathic pain model; however, it is unknown whether these effects involve autophagy induction. Methods We investigated the relationship between HRS and cell autophagy in a neuropathic pain model generated by chronic constriction injury (CCI) in Sprague–Dawley rats. Rats received an intraperitoneal injection of HRS (10 mL/kg daily, from 1 day before until 14 days after CCI), 3MA (autophagy inhibitor), 2ME2 (HIF-1α inhibitor), or EDHB (HIF-1α agonist). The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were tested 1 day before and 1, 3, 7, 10, and 14 days after the operation. HIF-1α and cell autophagy markers in the spinal cord were evaluated by western blotting and real-time PCR assays at 14 days after CCI. Autophagosomes with double membranes were identified by transmission electron microscopy. Results CCI caused behavioral hypersensitivity to mechanical and thermal stimulation in the hind-paw of the injured side. HRS improved MWT and TWL, activated autophagy, and increased autophagosomes and autolysosomes in CCI rats. 3-MA aggravated hyperalgesia and allodynia and suppressed autophagy, while EDHB attenuated hyperalgesia and activated the autophagy procedure and the HIF-1α downstream target gene BNIP3. HIF-1α inhibitors reversed the regulatory effects of HRS on autophagy in CCI rats at 14 days after spinal cord injury. Conclusion HRS reduced mechanical hyperalgesia and activation of cell autophagy in neuropathic pain through a HIF1-dependent pathway.

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Section: Introductionmentioning

confidence: 99%

Hydrogen-Rich Saline Activated Autophagy via HIF-1α Pathways in Neuropathic Pain Model

Wang

Huo

Chen

et al. 2018

BioMed Research International

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“…Treatment of neuropathic pain is challenging due to its varied etiology, symptoms and underlying mechanisms [ 1 2 ]. Uncertainty regarding the nature and exact location of the lesion, especially in non-specialist settings adds to this challenge.…”

Section: Introductionmentioning

confidence: 99%

Low doses of amitriptyline, pregabalin, and gabapentin are preferred for management of neuropathic pain in India: is there a need for revisiting dosing recommendations?

et al. 2017

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BackgroundCurrent therapy for the treatment of neuropathic pain is often unsatisfactory. Considerable variation in treatment pattern still exists in spite of availability of sufficient literature from various guidelines. Recent Indian market data suggested that the utilization (sale) of drugs such as amitriptyline, pregabalin, and gabapentin was more for low-dose unit packs than that of the high-dose unit packs, raising the belief that these drugs are prescribed at a lower dose than is actually recommended in the guidelines. To test this hypothesis, a survey was conducted across speciality throughout the country to observe the prescription pattern of these drugs amongst the health care providers in India.MethodsThree hundred fifty survey forms were distributed of which 281 forms were included for analysis.ResultsIt was observed that the commonly used initiation and maintenance dose for amitriptyline, pregabalin, and gabapentin was 5–10 mg/day, 50–75 mg/day, and 100–300 mg/day, respectively. The reason to select the lower dosages was to have a balancing effect to achieve good efficacy with minimum side effects. Care-givers reported no side effects/not many side effects as a reason in 22.2%, 16.88%, and 23.86% patients with amitriptyline, pregabalin, and gabapentin, respectively. Sedation and giddiness were commonly reported with all three drugs.ConclusionsCommonly prescribed drugs for management of neuropathic pain, such as amitriptyline, pregabalin, and gabapentin are preferred at lower doses in Indian clinical settings. Acceptable efficacy and low tolerance to the standard dosage is believed to be the reason behind the prescribed dose.

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“…We found that JMJD6 is primarily localized to neurons. Many studies have shown that spinal astrocytes are important in NPP (Gwak and Hulsebosch, 2009 ; Ikeda et al, 2012 ; Chen et al, 2014 ; Old et al, 2015 ), and miscommunication between neurons and glial cells, such as astrocytes and microglia, may also play a part in NPP (Chiang et al, 2012 ; Burke et al, 2016 ; Nascimento et al, 2016 ); however, we did not observe any significant JMJD6 localization to astrocytes or microglia. In this study, we conclude that JMJD6 does not localize to astrocytes or microglia.…”

Section: Discussionmentioning

confidence: 99%

“…A growing population worldwide are suffering symptoms of neuropathic pain (NPP), such as allodynia, hyperalgesia, or paresthesia, which are caused by lesions in the somatosensory nervous system (Treede et al, 2008 ; Geber et al, 2009 ; Haanpää et al, 2010 ). Many new therapies have been proposed, such as voltage-gated sodium or calcium channel blockers; however, there is currently a lack of effective and specific treatment options, which indicates that advancing our knowledge of the pathophysiology and the mechanisms underlying this type of pain is a priority (Chang et al, 2014 ; Schestatsky et al, 2014 ; Schug and Goddard, 2015 ; Nascimento et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Normalizing JMJD6 Expression in Rat Spinal Dorsal Horn Alleviates Hyperalgesia Following Chronic Constriction Injury

Wen

et al. 2018

Front. Neurosci.

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Jumonji domain-containing protein 6 (JMJD6) is a homolog of hypoxia-inducible factor (HIF) asparaginyl hydroxylase, an inhibitor of HIF. HIF-1α is known to participate in neuropathic pain (NPP) during chronic constriction injury (CCI); however, the roles of JMJD6 in NPP have not been systematically investigated. In this study, we examined the temporal distribution and cellular location of JMJD6 in the spinal cord during CCI. In addition, we assessed behavioral changes representative of NPP in rats. Following CCI, lentiviral vectors (LV-JMJD6) were intrathecally administered to observe the changes in the expression of JMJD6, HIF-1α, and its downstream factor caspase-3. Co-immunoprecipitation was used to detect potential interactions between JMJD6 and HIF-1α. We found that JMJD6 was decreased in rats following CCI, which was accompanied by significant NPP–associated behavioral changes. JMJD6 was mainly expressed in neurons. Intrathecal injection of LV-JMJD6 following CCI alleviated the thermal and mechanical hyperalgesia, normalized JMJD6 protein expression, and decreased HIF-1α protein expression with a corresponding reduction in caspase-3 protein expression. Furthermore, the co-immunoprecipitation analyses showed that JMJD6 and HIF-1α protein immunoprecipitated with each other, indicating an interaction between these two proteins. Taken together, the results suggest that JMJD6 may serve as a sensor in neurons of the adult rat spinal cord during the CCI state. Furthermore, JMJD6 may exert its function in NPP by regulating HIF-1α in rats exposed to CCI.

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Neuropathic pain treatment: still a challenge

Cited by 16 publications

References 27 publications

Hydrogen-Rich Saline Activated Autophagy via HIF-1α Pathways in Neuropathic Pain Model

Hydrogen-Rich Saline Activated Autophagy via HIF-1α Pathways in Neuropathic Pain Model

Low doses of amitriptyline, pregabalin, and gabapentin are preferred for management of neuropathic pain in India: is there a need for revisiting dosing recommendations?

Normalizing JMJD6 Expression in Rat Spinal Dorsal Horn Alleviates Hyperalgesia Following Chronic Constriction Injury

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