Chronic neuropathic pain after traumatic peripheral nerve injuries in the upper extremity: prevalence, demographic and surgical determinants, impact on health and on pain medication

AbstractBackground and aimsAside from the long term side effects of a nerve injury in the upper extremity with devastating consequences there is often the problem of chronic neuropathic pain. The studies concerning the prevalence of persistent pain of neuropathic origin after peripheral nerve injuries are sparse. The prevalence and risk factors associated with chronic neuropathic pain after nerve injuries in the upper extremity were assessed.MethodsA standardized data collection template was employed prospectively and retrospectively for all patients with traumatic nerve injuries accepted at the Hand Surgery Department, Uppsala, Sweden between 2010 and 2018. The template included demographic data, pain diagnosis, type of injured nerve, level of injury, date of the lesion and repair, type of procedure, reoperation, time since the procedure, S-LANSS questionnaire (Self report-Leeds Assessment of Neuropathic Symptoms and Signs), RAND-36 (Item short form health survey), QuickDASH (Disability of Shoulder, Arm and Hand) and additional questionnaires concerned medication, pain intensity were sent to 1,051 patients with nerve injuries. Partial proportional odds models were used to investigate the association between persistent pain and potential predictors.ResultsMore than half of the patients undergoing a surgical procedure developed persistent pain. Prevalence of neuropathic pain was 73% of the patients with pain (S-LANSS ≥ 12 or more). Multivariate analysis indicated that injury of a major nerve OR 1.6 (p = 0.013), years from surgery OR 0.91 (p = 0.01), younger age OR 0.7 (p < 0.001), were the main factors for predicting pain after surgery. The type of the nerve injured was the strongest predictor for chronic pain with major nerves associated with more pain (p = 0.019).ConclusionsA high prevalence of chronic pain and neuropathic pain with a negative impact on quality of life and disability were found in patients after traumatic nerve injury. Major nerve injury, younger age and less time from surgery were predictors for chronic pain.

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Relationship of Anti-interleukin-6 Receptor Antibody to Interleukin-6 Level and Inducible Nitrite Oxide Levels in Peripheral Nerve Injury in Chronic Constriction Injury-Induced Rats: A Case-Control Study in Indonesia

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2022.7604 ◽

2022 ◽

Vol 10 (A) ◽

pp. 1-5

Author(s):

Riki Sukiandra ◽

Eti Yerizel ◽

Yuliarni Syafrita ◽

Eryati Darwin

Keyword(s):

Neuropathic Pain ◽

Peripheral Nerve ◽

Nerve Injury ◽

Interleukin 6 ◽

Peripheral Nerve Injury ◽

Sandwich Elisa ◽

Peripheral Nerve Injuries ◽

Nerve Injuries ◽

Receptor Antibody ◽

Male Wistar Rats

BACKGROUND: Interleukin-6 (IL-6) and inducible Nitric oxide Synthase (iNOS) have an effect on neuropathic pain in the inflammatory process in peripheral nerve injuries. AIM: This study aims to examine the effect of anti-IL-6 receptor antibody on IL-6 and iNOS levels as a consideration for the treatment of neuropathic pain in a rat model of peripheral nerve injury. METHODS: Twenty-eight young adult male Wistar rats were treated for peripheral nerve injury and then divided into two groups. Fourteen treatment groups (Group P) were given anti-IL-6 receptor antibody by injection at a dose of 100 g/day by injection into the saphenous vein in the rat’s leg for 3 days. In both groups, the serum IL-6 and iNOS levels were assessed on the 3rd day after administration of anti-IL-6 receptor antibody in group P, using the sandwich ELISA method. RESULTS: The results showed that the administration of anti-IL-6 receptor antibody did not have a significant effect on reducing IL-6 and iNOS levels in group P (p > 0.05). Administration of anti-IL-6 receptor antibody had more effect on IL-6 levels on iNOS levels, where a decrease in IL-6 levels caused a decrease in iNOS levels in group P (p = 0.004 and r = 0.693). CONCLUSIONS: We conclude that the present administration of anti-IL-6 receptor antibody cannot be considered as a treatment for neuropathic pain in peripheral nerve injuries, but can be used to influence IL-6 levels on iNOS levels.

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Role of the immune system in neuropathic pain

Scandinavian Journal of Pain ◽

10.1515/sjpain-2019-0138 ◽

2019 ◽

Vol 20 (1) ◽

pp. 33-37 ◽

Cited By ~ 16

Author(s):

Marzia Malcangio

Keyword(s):

Spinal Cord ◽

Chronic Pain ◽

Nervous System ◽

Neuropathic Pain ◽

Immune System ◽

Peripheral Nerve ◽

Dorsal Horn ◽

Nerve Injury ◽

Immune Cells ◽

Peripheral Nerve Injury

AbstractBackgroundAcute pain is a warning mechanism that exists to prevent tissue damage, however pain can outlast its protective purpose and persist beyond injury, becoming chronic. Chronic Pain is maladaptive and needs addressing as available medicines are only partially effective and cause severe side effects. There are profound differences between acute and chronic pain. Dramatic changes occur in both peripheral and central pathways resulting in the pain system being sensitised, thereby leading to exaggerated responses to noxious stimuli (hyperalgesia) and responses to non-noxious stimuli (allodynia).Critical role for immune system cells in chronic painPreclinical models of neuropathic pain provide evidence for a critical mechanistic role for immune cells in the chronicity of pain. Importantly, human imaging studies are consistent with preclinical findings, with glial activation evident in the brain of patients experiencing chronic pain. Indeed, immune cells are no longer considered to be passive bystanders in the nervous system; a consensus is emerging that, through their communication with neurons, they can both propagate and maintain disease states, including neuropathic pain. The focus of this review is on the plastic changes that occur under neuropathic pain conditions at the site of nerve injury, the dorsal root ganglia (DRG) and the dorsal horn of the spinal cord. At these sites both endothelial damage and increased neuronal activity result in recruitment of monocytes/macrophages (peripherally) and activation of microglia (centrally), which release mediators that lead to sensitisation of neurons thereby enabling positive feedback that sustains chronic pain.Immune system reactions to peripheral nerve injuriesAt the site of peripheral nerve injury following chemotherapy treatment for cancer for example, the occurrence of endothelial activation results in recruitment of CX3C chemokine receptor 1 (CX3CR1)-expressing monocytes/macrophages, which sensitise nociceptive neurons through the release of reactive oxygen species (ROS) that activate transient receptor potential ankyrin 1 (TRPA1) channels to evoke a pain response. In the DRG, neuro-immune cross talk following peripheral nerve injury is accomplished through the release of extracellular vesicles by neurons, which are engulfed by nearby macrophages. These vesicles deliver several determinants including microRNAs (miRs), with the potential to afford long-term alterations in macrophages that impact pain mechanisms. On one hand the delivery of neuron-derived miR-21 to macrophages for example, polarises these cells towards a pro-inflammatory/pro-nociceptive phenotype; on the other hand, silencing miR-21 expression in sensory neurons prevents both development of neuropathic allodynia and recruitment of macrophages in the DRG.Immune system mechanisms in the central nervous systemIn the dorsal horn of the spinal cord, growing evidence over the last two decades has delineated signalling pathways that mediate neuron-microglia communication such as P2X4/BDNF/GABAA, P2X7/Cathepsin S/Fractalkine/CX3CR1, and CSF-1/CSF-1R/DAP12 pathway-dependent mechanisms.Conclusions and implicationsDefinition of the modalities by which neuron and immune cells communicate at different locations of the pain pathway under neuropathic pain states constitutes innovative biology that takes the pain field in a different direction and provides opportunities for novel approaches for the treatment of chronic pain.

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Permanent central synaptic disconnection of proprioceptors after nerve injury and regeneration. I. Loss of VGLUT1/IA synapses on motoneurons

Journal of Neurophysiology ◽

10.1152/jn.01095.2010 ◽

2011 ◽

Vol 106 (5) ◽

pp. 2450-2470 ◽

Cited By ~ 76

Author(s):

Francisco J. Alvarez ◽

Haley E. Titus-Mitchell ◽

Katie L. Bullinger ◽

Michal Kraszpulski ◽

Paul Nardelli ◽

...

Keyword(s):

Peripheral Nerve ◽

Nerve Injury ◽

Cell Body ◽

Peripheral Nerve Injury ◽

Motor Coordination ◽

Electrophysiological Study ◽

Peripheral Nerve Injuries ◽

Nerve Injuries ◽

Ia Afferent ◽

Axon Collaterals

Motor and sensory proprioceptive axons reinnervate muscles after peripheral nerve transections followed by microsurgical reattachment; nevertheless, motor coordination remains abnormal and stretch reflexes absent. We analyzed the possibility that permanent losses of central IA afferent synapses, as a consequence of peripheral nerve injury, are responsible for this deficit. VGLUT1 was used as a marker of proprioceptive synapses on rat motoneurons. After nerve injuries synapses are stripped from motoneurons, but while other excitatory and inhibitory inputs eventually recover, VGLUT1 synapses are permanently lost on the cell body (75–95% synaptic losses) and on the proximal 100 μm of dendrite (50% loss). Lost VGLUT1 synapses did not recover, even many months after muscle reinnervation. Interestingly, VGLUT1 density in more distal dendrites did not change. To investigate whether losses are due to VGLUT1 downregulation in injured IA afferents or to complete synaptic disassembly and regression of IA ventral projections, we studied the central trajectories and synaptic varicosities of axon collaterals from control and regenerated afferents with IA-like responses to stretch that were intracellularly filled with neurobiotin. VGLUT1 was present in all synaptic varicosities, identified with the synaptic marker SV2, of control and regenerated afferents. However, regenerated afferents lacked axon collaterals and synapses in lamina IX. In conjunction with the companion electrophysiological study [Bullinger KL, Nardelli P, Pinter MJ, Alvarez FJ, Cope TC. J Neurophysiol (August 10, 2011). doi:10.1152/jn.01097.2010], we conclude that peripheral nerve injuries cause a permanent retraction of IA afferent synaptic varicosities from lamina IX and disconnection with motoneurons that is not recovered after peripheral regeneration and reinnervation of muscle by sensory and motor axons.

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Tendon transfers for upper extremity peripheral nerve injuries

Current Orthopaedics ◽

10.1016/0268-0890(91)90048-5 ◽

1991 ◽

Vol 5 (2) ◽

pp. 84-87

Author(s):

M.Mark Hoffer

Keyword(s):

Peripheral Nerve ◽

Upper Extremity ◽

Peripheral Nerve Injuries ◽

Nerve Injuries ◽

Tendon Transfers

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Comparative Strength of Muscles with Similar Function: A Study on Peripheral Nerve Injuries of the Upper Extremity

Physical Therapy ◽

10.1093/ptj/26.2.59 ◽

1946 ◽

Vol 26 (2) ◽

pp. 59-65

Author(s):

Signe Brunnstrom

Keyword(s):

Peripheral Nerve ◽

Upper Extremity ◽

Peripheral Nerve Injuries ◽

Similar Function ◽

Nerve Injuries

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Nerve Injuries from Positioning and Regional Blocks

10.1093/med/9780190226459.003.0074 ◽

2017 ◽

Author(s):

Rajnish K. Gupta ◽

Alexandria N. Nickless

Keyword(s):

Peripheral Nerve ◽

Nerve Injury ◽

Perioperative Period ◽

Peripheral Nerve Injuries ◽

Nerve Injuries ◽

Close Attention ◽

Anesthetic Complications ◽

Actual Incidence ◽

Attention To Detail

Peripheral nerve injury in the perioperative period can have a variety of etiologies, including preexisting patient factors and by surgical and anesthetic complications such as intraoperative positioning and nerve blockade. The actual incidence may be difficult to assess, because most nerve injuries resolve with time and frequently require minimal to no intervention. Injuries often manifest more than 48 hours after surgery and have even been noted in patients who undergo awake procedures and in hospitalized patients who never undergo surgery. This should not negate the fact that close attention to detail when positioning patients and performing regional anesthesia may help decrease the overall incidence of nerve injury and should be considered in every anesthesiologist’s perioperative plan. This chapter reviews proper assessment, treatment, and follow-up for peripheral nerve injuries.

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Clinical outcome and ultrasonographic evaluation of treatment using polyglycolic acid-collagen tube for chronic neuropathic pain after peripheral nerve injury

Journal of Orthopaedic Science ◽

10.1016/j.jos.2019.07.017 ◽

2019 ◽

Vol 24 (6) ◽

pp. 1064-1067

Author(s):

Mineyuki Zukawa ◽

Ryusuke Osada ◽

Tomoatsu Kimura

Keyword(s):

Neuropathic Pain ◽

Clinical Outcome ◽

Peripheral Nerve ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Polyglycolic Acid ◽

Chronic Neuropathic Pain

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Recovery of Peripheral Nerve with Massive Loss Defect by Tissue Engineered Guiding Regenerative Gel

BioMed Research International ◽

10.1155/2014/327578 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 9

Author(s):

Shimon Rochkind ◽

Zvi Nevo

Keyword(s):

Peripheral Nerve ◽

Nerve Regeneration ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Preclinical Study ◽

Significant Loss ◽

Peripheral Nerve Injuries ◽

Nerve Injuries ◽

Reconstructive Procedures ◽

Nerve Conduits

Objective. Guiding Regeneration Gel (GRG) was developed in response to the clinical need of improving treatment for peripheral nerve injuries and helping patients regenerate massive regional losses in peripheral nerves. The efficacy of GRG based on tissue engineering technology for the treatment of complete peripheral nerve injury with significant loss defect was investigated.Background. Many severe peripheral nerve injuries can only be treated through surgical reconstructive procedures. Such procedures are challenging, since functional recovery is slow and can be unsatisfactory. One of the most promising solutions already in clinical practice is synthetic nerve conduits connecting the ends of damaged nerve supporting nerve regeneration. However, this solution still does not enable recovery of massive nerve loss defect.The proposed technologyis a biocompatible and biodegradable gel enhancing axonal growth and nerve regeneration. It is composed of a complex of substances comprising transparent, highly viscous gel resembling the extracellular matrix that is almost impermeable to liquids and gasses, flexible, elastic, malleable, and adaptable to various shapes and formats.Preclinical studyon rat model of peripheral nerve injury showed that GRG enhanced nerve regeneration when placed in nerve conduits, enabling recovery of massive nerve loss, previously unbridgeable, and enabled nerve regeneration at least as good as with autologous nerve graft “gold standard” treatment.

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