Clinical evidence and mechanisms of growth factors in idiopathic and diabetes-induced carpal tunnel syndrome

Sharma, Deepankshi; Jaggi, Amteshwar Singh; Bali, Anjana

doi:10.1016/j.ejphar.2018.08.017

Cited by 19 publications

(17 citation statements)

References 63 publications

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“…Furthermore, relevant to compressive median mononeuropathies, several groups have already identified the presence of CCN2 in fibrotic and thickened subsynovial specimens collected from patients with idiopathic median mononeuropathy during release surgeries 1,34,35 . Treatment of cultured subsynovial specimens collected from patients with idiopathic median mononeuropathy with TGFbeta receptor inhibitors has been shown to down regulate fibrotic gene expression in those ex vivo tissues, indicating that blocking TGFbeta signaling may be an important approach to the treatment of perineural fibrosis in this patient population.…”

Section: Discussionmentioning

confidence: 99%

Blocking CTGF/CCN2 reverses neural fibrosis and sensorimotor declines in a rat model of overuse‐induced median mononeuropathy

Barbe

Hilliard

Amin

et al. 2020

Journal Orthopaedic Research

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Encapsulation of median nerves is a hallmark of overuse-induced median mononeuropathy and contributes to functional declines. We tested if an antibody against CTGF/CCN2 (termed FG-3019 or Pamrevlumab) reduces established neural fibrosis and sensorimotor declines in a clinically relevant rodent model of overuse in which median mononeuropathy develops. Young adult female rats performed a high repetition high force (HRHF) lever-pulling task for 18 weeks. Rats were then euthanised at 18 weeks (HRHF untreated), or rested and systemically treated for 6 weeks with either an anti-CCN2 monoclonal antibody (HRHF-Rest/FG-3019) or IgG (HRHF-Rest/IgG), with results compared with nontask control rats. Neuropathology was evident in HRHF-untreated and HRHF-Rest/IgG rats as increased perineural collagen deposition and degraded myelin basic protein (dMBP) in median nerves, and increased substance P in lower cervical dorsal root ganglia (DRG), compared with controls. Both groups showed functional declines, specifically, decreased sensory conduction velocity in median nerves, noxious cold temperature hypersensitivity, and grip strength declines, compared with controls. There were also increases of ATF3-immunopositive nuclei in ventral horn neurons in HRHFuntreated rats, compared with controls (which showed none). FG-3019-treated rats showed no increase above control levels of perineural collagen or dMBP in median nerves, Substance P in lower cervical DRGs, or ATF3-immunopositive nuclei in ventral horns, and similar median nerve conduction velocities and thermal sensitivity, compared with controls. We hypothesize that neural fibrotic processes underpin the sensorimotor declines by compressing or impeding median nerves during movement, and that inhibiting fibrosis using an anti-CCN2 treatment reverses these effects.

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Section: Discussionmentioning

confidence: 99%

Blocking CTGF/CCN2 reverses neural fibrosis and sensorimotor declines in a rat model of overuse‐induced median mononeuropathy

Barbe

Hilliard

Amin

et al. 2020

Journal Orthopaedic Research

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“…It is a multifunctional protein involved in the pathogenesis of chronic inflammation and fibrosis . Interleukins are molecules that act as growth factors for inflammatory and immune cells . An increase in mechanical pressure in the wrist increases the release of interleukins (IL‐1, IL‐2, and IL‐6).…”

Section: Discussionmentioning

confidence: 99%

“…An increase in mechanical pressure in the wrist increases the release of interleukins (IL‐1, IL‐2, and IL‐6). These elevated levels of interleukins increase the expression of growth factors, including TGF‐β and vascular endothelial growth factor (VEGF) . Chikenji et al reported that in patients with idiopathic CTS, connective tissue growth factor (CTGF) expression increased with TGF‐β, which plays a role in the pathogenesis of fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…These elevated levels of interleukins increase the expression of growth factors, including TGF-β and vascular endothelial growth factor (VEGF). 27 Chikenji et al 4 reported that in patients with idiopathic CTS, connective tissue growth factor (CTGF) expression increased with TGF-β, which plays a role in the pathogenesis of fibrosis. CTGF expression is rapidly induced by the action of TGF-β in mesenchymalderived cells and is effective in the formation of fibrosis.…”

Section: Discussionmentioning

confidence: 99%

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Correlation of neutrophil/lymphocyte and platelet/lymphocyte ratios with the severity of idiopathic carpal tunnel syndrome

Güneş

Büyükgöl

2020

Muscle and Nerve

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Background The aim of the present study was to investigate the correlation of the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio with the severity of idiopathic carpal tunnel syndrome (CTS). Methods A total of 407 patients with idiopathic CTS (neurophysiologically 150 mild, 144 moderate, and 113 severe) and 206 subjects without CTS were included (control group). Results There was a positive correlation between the severity of CTS and NLR (r = 0.224; P < 0.001), age (r = 0.333; P < 0.001), and body mass index (r = 0.251; P < 0.001). A 1‐unit increase in NLR level was associated with an approximately 1.7‐fold higher incidence of CTS (P = 0.002; odds ratio = 1.668; 95% confidence interval = 1.199‐2.319). Conclusions Our results suggest that neurophysiologically more severe CTS is associated with higher NLR levels. The role of systemic inflammation in CTS should be investigated in further studies.

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“…Histologically, there is median nerve and connective tissue subsynovial fibrosis due to increased periods of high pressure in the carpal tunnel. Cytokines that mediate inflammation, such as IL1 and IL6, and TGF‐β play a key role in CTS fibrosis (Sharma, Jaggi, & Bali, 2018). Therefore, an inflammatory fibrosis cannot be ruled out in the progression and recurrence of CTS disease.…”

Section: Introductionmentioning

confidence: 99%

Comparison of amniotic membrane transplantation and carpal tunnel syndrome release surgery (CTRS) and CTRS alone: Clinical outcomes at 1‐year follow‐up

Buentello-Volante

Molina‐Medinilla

Aguayo‐Flores

et al. 2020

J Tissue Eng Regen Med

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Carpal tunnel syndrome (CTS) is the most common focal entrapment mononeuropathy, comprising medium nerve chronic inflammation and fibrosis.Although carpal tunnel release surgery (CTRS) has demonstrated to be effective, around 3% to 25% of CTRS show recurrence. Amniotic membrane transplantation (AMT) has been used in different pathologies inhibiting inflammation and fibrosis and promoting nerve repair. The aim of this study was to determine the efficacy of AMT in CTRS. The present study comprised a randomized, single-blind controlled trial to compare the 1-year follow-up outcomes of AMT in CTRS (AMT group) or CTRS alone (control group) in patients with CTS. Thirty-five patients with unilateral or bilateral CTS were enrolled, and 47 wrists were randomized into two groups: the AMT group and the control group. To compare the outcomes, three different questionnaires scores (Boston Carpal Tunnel Syndrome Questionnaire, Disabilities of the Arm, Shoulder, and Hand, and Historical-Objective scale) were used. Evaluations were assessed at baseline and at 15 days, 1, 3, 6, and 12 months after surgery. Compared with the control group, the AMT group showed significant (p < 0.05) reductions in all scores from 6 months after surgery until the end of the study. Both AMT and control groups showed significant intragroup differences in all scores, since the first month after surgery until the end of the study in comparison with the baseline scores. Taken together, these results indicate that CTRS in conjunction with AMT is more effective than CTRS alone in patients with CTS at 1-year follow-up.

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Clinical evidence and mechanisms of growth factors in idiopathic and diabetes-induced carpal tunnel syndrome

Cited by 19 publications

References 63 publications

Blocking CTGF/CCN2 reverses neural fibrosis and sensorimotor declines in a rat model of overuse‐induced median mononeuropathy

Blocking CTGF/CCN2 reverses neural fibrosis and sensorimotor declines in a rat model of overuse‐induced median mononeuropathy

Correlation of neutrophil/lymphocyte and platelet/lymphocyte ratios with the severity of idiopathic carpal tunnel syndrome

Comparison of amniotic membrane transplantation and carpal tunnel syndrome release surgery (CTRS) and CTRS alone: Clinical outcomes at 1‐year follow‐up

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