Cytotoxic Immunity in Peripheral Nerve Injury and Pain

Davies, AN; Rinaldi, Simon; Costigan, Michael; Oh, Seog Bae

doi:10.3389/fnins.2020.00142

Cited by 57 publications

(54 citation statements)

References 299 publications

(361 reference statements)

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“…31,32 It has been suggested that a disequilibrium between degenerative and regenerative processes along with (over)expression of neurotrophic factors following nerve injury can lead to neuropathic pain. [33][34][35] Phantom limb pain is thought to be the result of maladaptive cortical, subcortical, and spinal reorganization after nerve injury, a reflection of neuroplasticity. [36][37][38] It is unclear if subcortical and peripheral changes induce and maintain cortical changes, but it may be the reason why TMR appears to be less effective in patients with long-standing phantom limb pain.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Neuropathic Pain Following Major Upper Extremity Amputation

Lans

Hoftiezer

Lozano-Calderón

et al. 2020

J Reconstr Microsurg

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Background Active treatment (targeted muscle reinnervation [TMR] or regenerative peripheral nerve interfaces [RPNIs]) of the amputated nerve ends has gained momentum to mitigate neuropathic pain following amputation. Therefore, the aim of this study is to determine the predictors for the development of neuropathic pain after major upper extremity amputation. Methods Retrospectively, 142 adult patients who underwent 148 amputations of the upper extremity between 2000 and 2019 were identified through medical chart review. All upper extremity amputations proximal to the metacarpophalangeal joints were included. Patients with a follow-up of less than 6 months and those who underwent TMR or RPNI at the time of amputation were excluded. Neuropathic pain was defined as phantom limb pain or a symptomatic neuroma reported in the medical charts at 6 months postoperatively. Most common indications for amputation were oncology (n = 53, 37%) and trauma (n = 45, 32%), with transhumeral amputations (n = 44, 30%) and shoulder amputations (n = 37, 25%) being the most prevalent. Results Neuropathic pain occurred in 42% of patients, of which 48 (32%) had phantom limb pain, 8 (5.4%) had a symptomatic neuroma, and 6 (4.1%) had a combination of both. In multivariable analysis, traumatic amputations (odds ratio [OR]: 4.1, p = 0.015), transhumeral amputations (OR: 3.9, p = 0.024), and forequarter amputations (OR: 8.4, p = 0.003) were independently associated with the development of neuropathic pain. Conclusion In patients with an upper extremity amputation proximal to the elbow or for trauma, there is an increased risk of developing neuropathic pain. In these patients, primary TMR/RPNI should be considered and this warrants a multidisciplinary approach involving general trauma surgeons, orthopaedic surgeons, plastic surgeons, and vascular surgeons.

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Section: Discussionmentioning

confidence: 99%

Risk Factors for Neuropathic Pain Following Major Upper Extremity Amputation

Lans

Hoftiezer

Lozano-Calderón

et al. 2020

J Reconstr Microsurg

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“…This mechanism, whereby extrinsic pruritogen increases itch afferent signaling, applies to neuropathic itch in certain clinical contexts. After peripheral nerve injury, significant inflammation concurrently develops with sensory abnormalities ( Figure 1 ) [ 4 , 18 ]. Itch neurons express a variety of receptors for inflammatory mediators such as proteases, tryptase, chymase, and cathepsin, and cytokines, thymic stromal lymphopoietin, interleukin (IL)-4, 13, 31, and 33 [ 16 , 19 , 20 , 21 , 22 , 23 ].…”

Section: Neuropathic Itch and Inflammationmentioning

confidence: 99%

Neuropathic Itch

Meixiong

Dong

Weng

2020

Cells

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Neurologic insults as varied as inflammation, stroke, and fibromyalgia elicit neuropathic pain and itch. Noxious sensation results when aberrantly increased afferent signaling reaches percept-forming cortical neurons and can occur due to increased sensory signaling, decreased inhibitory signaling, or a combination of both processes. To treat these symptoms, detailed knowledge of sensory transmission, from innervated end organ to cortex, is required. Molecular, genetic, and behavioral dissection of itch in animals and patients has improved understanding of the receptors, cells, and circuits involved. In this review, we will discuss neuropathic itch with a focus on the itch-specific circuit.

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“…In addition, local administration of IL-17 is associated with increased numbers of activated dendritic cells and infiltrating neutrophils at the site of the injected hind paws, and increased neutrophil infiltration in the injected sciatic nerves [121]. While it is known that CD8 + cytotoxic T cells are recruited to peripherally injured nerves, responding to elevated antigen-presenting MHC class I molecules, the precise mechanism underlying this process remains unclear ( [122,123]; reviewed in [124]). It was recently shown that Treg cells also play a role at the site of a peripheral nerve injury, counteracting neuropathic pain by inhibiting Th1 cell-mediated responses [125], and it has been reported that there is a disrupted Th17/Treg balance in patients with chronic low back pain [126].…”

Section: At the Site Of The Peripherally Injured Sciatic Nerve And Asmentioning

confidence: 99%

Sex differences in neuro(auto)immunity and chronic sciatic nerve pain

2020

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Chronic pain occurs with greater frequency in women, with a parallel sexually dimorphic trend reported in sufferers of many autoimmune diseases. There is a need to continue examining neuro-immune-endocrine crosstalk in the context of sexual dimorphisms in chronic pain. Several phenomena in particular need to be further explored. In patients, autoantibodies to neural antigens have been associated with sensory pathway hyper-excitability, and the role of self-antigens released by damaged nerves remains to be defined. In addition, specific immune cells release pro-nociceptive cytokines that directly influence neural firing, while T lymphocytes activated by specific antigens secrete factors that either support nerve repair or exacerbate the damage. Modulating specific immune cell populations could therefore be a means to promote nerve recovery, with sex-specific outcomes. Understanding biological sex differences that maintain, or fail to maintain, neuroimmune homeostasis may inform the selection of sex-specific treatment regimens, improving chronic pain management by rebalancing neuroimmune feedback. Given the significance of interactions between nerves and immune cells in the generation and maintenance of neuropathic pain, this review focuses on sex differences and possible links with persistent autoimmune activity using sciatica as an example.

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Cytotoxic Immunity in Peripheral Nerve Injury and Pain

Cited by 57 publications

References 299 publications

Risk Factors for Neuropathic Pain Following Major Upper Extremity Amputation

Risk Factors for Neuropathic Pain Following Major Upper Extremity Amputation

Neuropathic Itch

Sex differences in neuro(auto)immunity and chronic sciatic nerve pain

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