Cytokine Antagonism Reduces Pain and Modulates Spinal Astrocytic Reactivity After Cervical Nerve Root Compression

Rothman, Sarah M.; Winkelstein, Beth A.

doi:10.1007/s10439-010-0012-8

Cited by 36 publications

(45 citation statements)

References 57 publications

(78 reference statements)

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“…124 135 Comparative effectiveness studies by one group showed similar benefit in pain relief, function, and other outcome measures such as opioid consumption and employment for both steroids and local anesthetic in a variety of cervical diseases including disc hernation. [120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135][136][137][138] Another randomized study in 169 patients with radicular pain found the combination of ESI and conservative treatment consisting of physical therapy and the adjuvants nortriptyline or gabapentin (or both) provided superior relief compared with either treatment alone (mean reduction in pain score of 3.1 in the combination group versus 1.9 in the others at one month; P=0.035). 139 Together, these studies provide limited evidence that ESI is more effective than epidural non-steroid injections but moderate evidence that a series of epidural injections can provide sustained relief.…”

Section: Cervical Discogenic Painmentioning

confidence: 99%

Advances in the diagnosis and management of neck pain

Cohen

Hooten

2017

BMJ

226

182

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Neck pain imposes a considerable personal and socioeconomic burden-it is one of the top five chronic pain conditions in terms of prevalence and years lost to disability-yet it receives a fraction of the research funding given to low back pain. Although most acute episodes resolve spontaneously, more than a third of affected people still have low grade symptoms or recurrences more than one year later, with genetics and psychosocial factors being risk factors for persistence. Nearly half of people with chronic neck pain have mixed neuropathic-nociceptive symptoms or predominantly neuropathic symptoms. Few clinical trials are dedicated solely to neck pain. Muscle relaxants and non-steroidal anti-inflammatory drugs are effective for acute neck pain, and clinical practice is mostly guided by the results of studies performed for other chronic pain conditions. Among complementary and alternative treatments, the strongest evidence is for exercise, with weaker evidence supporting massage, acupuncture, yoga, and spinal manipulation in different contexts. For cervical radiculopathy and facet arthropathy, weak evidence supports epidural steroid injections and radiofrequency denervation, respectively. Surgery is more effective than conservative treatment in the short term but not in the long term for most of these patients, and clinical observation is a reasonable strategy before surgery.

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Section: Cervical Discogenic Painmentioning

confidence: 99%

Advances in the diagnosis and management of neck pain

Cohen

Hooten

2017

BMJ

226

182

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“…3 Whiplash is a common cause of chronic neck pain, and the cervical facet joint has been identified as the site of pain in the majority of these cases. 1 Although anesthetic facet joint blocks, application of cytokine antagonists, and corticosteroid injections can provide temporary pain relief for some individuals, 1,9,26 up to 62% of people affected by whiplash injuries report pain lasting 2 years or more after injury. 6 Developing a fundamental understanding of facet joint injuries, and how to treat them following whiplash, has been impeded by the lack of radiographic or magnetic resonance imaging (MRI) evidence of any injury to the structures of the neck in most whiplash patients.…”

Section: Introductionmentioning

confidence: 99%

Detection of Altered Collagen Fiber Alignment in the Cervical Facet Capsule After Whiplash-Like Joint Retraction

Quinn

Winkelstein

2011

Ann Biomed Eng

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The cervical facet joint has been identified as the source of pain in patients with whiplash-associated disorders, but most clinical studies report no radiographic evidence of tissue injury in these disorders. The goal of this study was to utilize quantitative polarized light imaging to assess the potential for altered collagen fiber alignment in human cadaveric cervical facet capsule specimens (n = 8) during and after a joint retraction simulating whiplash exposure. Although no evidence of ligament damage was detected during whiplash-like retraction, mechanical and microstructural changes were identified after loading. Retraction produced significant decreases in ligament stiffness (p = 0.0186) and increases in laxity (p = 0.0065). In addition, image analysis indicated that 21.1 ± 17.1% of the capsule sustained principal strains that were unrecovered immediately after retraction. Altered collagen fiber alignment was detected in 32.7 ± 22.9% of the capsule after retraction. The capsule regions with unrecovered strain and altered fiber alignment after retraction were significantly co-localized with each other (p < 0.0001), suggesting the altered mechanical function may relate to a change in the tissue's fiber organization. The identification of altered fiber alignment in this ligament following retraction without any tears implicates the whiplash kinematic as a potential cause of microstructural damage that is not detectable using standard clinical imaging techniques.

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“…Images were cropped to include a region of interest in the superficial dorsal horn before GFAP or PAR1 expression was quantified using a customized densitometry program created in MATLAB (matrix laboratory), as previously reported. 12,44,47,48 Briefly, spinal cord sections were imaged at 20X magnification, and images were cropped to a uniform region of interest including only the dorsal horn tissue. Cropped images were then inverted, and the percentage of pixels above a pre-defined threshold was measured.…”

Section: Methodsmentioning

confidence: 99%

Ketorolac Reduces Spinal Astrocytic Activation and PAR1 Expression Associated with Attenuation of Pain after Facet Joint Injury

Dong

Smith²,

Winkelstein³

2013

Journal of Neurotrauma

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Chronic neck pain affects up to 70% of persons, with the facet joint being the most common source. Intra-articular injection of the non-steroidal anti-inflammatory drug ketorolac reduces post-operative joint-mediated pain; however, the mechanism of its attenuation of facet-mediated pain has not been evaluated. Protease-activated receptor-1 (PAR1) has differential roles in pain maintenance depending on the type and location of painful injury. This study investigated if the timing of intra-articular ketorolac injection after painful cervical facet injury affects behavioral hypersensitivity by modulating spinal astrocyte activation and/or PAR1 expression. Rats underwent a painful joint distraction and received an injection of ketorolac either immediately or 1 day later. Separate control groups included injured rats with a vehicle injection at day 1 and sham operated rats. Forepaw mechanical allodynia was measured for 7 days, and spinal cord tissue was immunolabeled for glial fibrillary acidic protein (GFAP) and PAR1 expression in the dorsal horn on day 7. Ketorolac administered on day 1 after injury significantly reduced allodynia ( p = 0.0006) to sham levels, whereas injection immediately after the injury had no effect compared with vehicle. Spinal astrocytic activation followed behavioral responses and was significantly decreased ( p = 0.009) only for ketorolac given at day 1. Spinal PAR1 ( p = 0.0025) and astrocytic PAR1 ( p = 0.012) were significantly increased after injury. Paralleling behavioral data, astrocytic PAR1 was returned to levels in sham only when ketorolac was administered on day 1. Yet, spinal PAR1 was significantly reduced ( p < 0.0001) by ketorolac independent of timing. Spinal astrocyte expression of PAR1 appears to be associated with the maintenance of facet-mediated pain.

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Cytokine Antagonism Reduces Pain and Modulates Spinal Astrocytic Reactivity After Cervical Nerve Root Compression

Cited by 36 publications

References 57 publications

Advances in the diagnosis and management of neck pain

Advances in the diagnosis and management of neck pain

Detection of Altered Collagen Fiber Alignment in the Cervical Facet Capsule After Whiplash-Like Joint Retraction

Ketorolac Reduces Spinal Astrocytic Activation and PAR1 Expression Associated with Attenuation of Pain after Facet Joint Injury

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