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Neuropathic pain: overview and research tools

Related

  • Neuroscience resources
    • Ion channels: webinars
      • Neuroinflammation
        • Neural markers
          • Agonists, antagonists, activators and inhibitors
            • Ion channel modulators
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                  ​​Get to the root of neuropathic pain with high-quality, reliable research products, including recombinant monoclonal antibodies, bioactive proteins, and SimpleStep® ELISA kits.

                  ​Published February 1, 2021 

                  Contents  

                  • What is neuropathic pain?
                  • Inflammation in the pathophysiology of neuropathic pain
                    • Role of pro-inflammatory cytokines
                    • Role of anti-inflammatory cytokines
                    • Neuroinflammation in chronic pain
                  • Roles of receptors and ion channels in neuropathic pain
                    • The transient receptor potential (TRP) ion channels
                    • Sodium ion channels
                  • Antibodies, proteins, and kits for neuropathic pain research
                    • Monoclonal antibodies for key ion channels and receptors in neuropathic pain
                    • Biochemicals targeting ion channels
                    • Research tools for neuropeptides
                    • Research tools for inflammatory markers and growth factors
                    • Recombinant monoclonal antibodies for key cellular and neuronal markers
                  • References

                  ​

                  What is neuropathic pain?

                  Neuropathic pain is a chronic pain caused by a lesion or disease of the somatosensory system, including peripheral fibers and central neurons, affecting 7-10% of the general population1. Many factors are implicated in the development of neuropathic pain, such as imbalances between excitatory and inhibitory somatosensory signaling, alterations in ion channels, and variability in the modulation of pain messages in the central nervous system1.  

                  Numerous diseases may cause neuropathic pain, including autoimmune diseases (eg, multiple sclerosis), neurodegenerative diseases (eg, Parkinson’s disease), metabolic diseases (eg, diabetic neuropathy), infection, vascular disease (stroke), trauma, and cancer.

                  ​​​​​​Inflammation in the pathophysiology of neuropathic pain​

                  The immune system and inflammatory response appear to play a crucial role in the mediation of neuropathic pain. Many diverse causes of neuropathic pain (eg, spinal cord injury) are linked to excessive inflammation in both the peripheral and central nervous system, which may contribute to both the initiation and maintenance of persistent pain. 

                  Role of pro-inflammatory cytokines

                  Elevated pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IL-17, are associated with neuropathic pain. They have been found to increase in animal models of neuropathic pain and the cerebrospinal fluid (CSF) and blood of patients with chronic neuropathic pain. Furthermore, both animal models and clinical studies showed that pharmacologically lowering pro-inflammatory cytokines' levels may reduce pain.

                  TNF-α has been widely studied in neuropathic pain, and several TNF-α inhibitors are currently FDA-approved for painful disorders, including inflammatory bowel disease and rheumatoid arthritis. However, randomized clinical trials have failed to establish the clinical efficacy of TNF-α inhibitors in neuropathic pain, despite the promising early studies.

                  Role of anti-inflammatory cytokines

                  In contrast to pro-inflammatory cytokines, anti-inflammatory cytokines, such as IL-4, IL-10, TGF-β, are linked to downregulation of the immune system and neuropathic pain relief11. Reduced levels of anti-inflammatory cytokines have been found in patients with chronic neuropathic pain conditions. Although anti-inflammatory cytokines offer an exciting new therapeutic opportunity for neuropathic pain, the current scientific evidence is limited to in vitro and animal studies.

                  Neuroinflammation in chronic pain

                  Neuroinflammation, characterized by glial cell activation, leukocyte infiltration, and the production of inflammatory mediators, has been suggested to play a crucial role in the induction and maintenance of different types of chronic pain, including neuropathic pain. Several emerging targets have been shown to contribute to neuroinflammation and chronic pain sensitization by regulating neuron-glia interactions in the spinal cord. This includes chemokines (CXCL1, CCL2, and CX3CL1), proteases (MMP9, cathepsin S, and cas­pase 6), and the WNT signaling pathway.

                  Role of receptors and ion channels in neuropathic pain

                  Nociceptive neurons serve as mediators in painful stimulus transmission between the central and peripheral nervous systems. These neurons express various receptors and ion channels that can detect and process noxious stimuli, including pain signals2.

                  Several studies indicate that dysregulation of neurotransmitters and over-excitation of ion channels responsible for signal transmission may contribute to the sensation of neuropathic pain3,4. Also, current first-line pharmacological treatments against neuropathic pain, such as antidepressants and anticonvulsants, target specific neurotransmitter receptors and ion channels5.

                  The transient receptor potential (TRP) ion channels

                  The transient receptor potential (TRP) ion channels belong to the most important ion channel family that detects and transmits noxious stimuli. TRP family includes conserved nonselective calcium-permeable channels that act as molecular sensors of multiple stimuli, such as pH changes, chemical agents, temperature, and osmolarity2.

                  Several TRP ion channels, including TRPV1, TRPV4, and TRPM8, have been linked to neuropathic pain conditions in animal models. For example, pharmacological inhibition of TRPV1 was shown to decrease pain in several animal models of neuropathic pain6,7, while activation of the TRPM8 channel can generate analgesia in chronic neuropathic pain in rats8. 

                  Sodium ion channels

                  Several types of voltage-gated sodium channels (including NaV1.3, NaV1.7, NaV1.8) may be involved in neuropathic pain as their expression is changed during neuropathic pain, and their block shows therapeutic utility9. These channels are found in the dorsal root ganglion cells and therefore are likely involved in action potential generation and conduction in nociceptors. However, the specific contribution of each of those sodium channels to neuropathic pain remains unclear9,10.

                  Antibodies, proteins, and kits for neuropathic pain research

                  To help you identify the best tools for your neuropathic pain research, we’ve compiled a list of our high-quality antibodies, proteins, and SimpleStep® ELISA kits for the key targets in neuropathic pain.

                  Monoclonal antibodies for key ion channels and receptors in neuropathic pain

                  Here we recommend our specific monoclonal antibodies for key targets in neuropathic pain research, including TRP and sodium ion channels. Our neuropathic pain portfolio includes many recombinant monoclonal RabMAb® antibodies that give you the highest level of batch-to-batch consistency, unrivaled reproducibility, confirmed specificity, and a guaranteed long-term supply. 


                   Category

                  Gene name

                  Target name

                  Recommended abID

                  Species

                  Application

                  Transient Receptor Potential (TRP)


                  TRPV1

                  Transient receptor potential cation channel subfamily V member 1

                  ab203103

                  Mouse, Rat

                  WB, IHC-Fr, ICC/IF, Flow Cyt

                  TRPV4

                  Transient receptor potential cation channel subfamily V member 4

                  ab231772


                  Mouse, Rat

                  IHC-P

                  TRPM8

                  Transient receptor potential cation channel subfamily M member 8

                  ab109308

                  Mouse, Human

                  WB

                  Sodium channels

                  SCN9A

                  NaV1.7 (Sodium channel protein type 9 subunit alpha)

                  ab85015

                  Mouse, Rat, Human

                  IHC-P, Flow Cyt

                  SCN10A

                  NaV1.8 (Sodium channel protein type 10 subunit alpha)

                  ab93616

                   Mouse, Rat, Human, Monkey

                  WB, IHC-P, Flow Cyt

                  Purinoceptors

                  P2RX7

                  P2X purinoceptor 7

                  ab195356

                  Mouse

                   Flow Cyt, IHC-Fr

                  Other receptors

                  NMDAR 2B

                  Glutamate receptor ionotropic, NMDA 2B, GluN2B

                  ab254356

                  Mouse, Rat, Human

                  WB, IHC-P, IP

                  OPRM1

                  Mu-type opioid receptor, M-OR-1

                  ab134054

                  Mouse, Rat, Human

                  WB


                  Biochemicals targeting ion channels


                  Compound name 

                  Function 

                  AbID 

                  Tetrodotoxin citrate 

                  Na+ channel blocker 

                  ab120055 

                  WS 12 

                  TRPM8 agonist 

                  ab145195 

                  Brilliant Blue G 

                  non-competitive P2X7 antagonist 

                  ab120389 

                  Ifenprodil hemitartrate 

                  GluN2B (formerly NR2B)-preferring NMDA antagonist 

                  ab120111 

                  AMG 9810 

                  TRPV1 receptor antagonist 

                  ab145874 


                  ​​Research tools for neuropeptides

                  Changes in neuropeptide synthesis and release have been linked to the pain symptoms that follow chronic inflammation and neuropathic injuries. Find the right tools to investigate the role of neuropeptides in neuropathic pain.


                  Gene

                  Target

                  Recommended antibody

                  Peptide

                  ELISA kit

                  TAC1

                  Protachykinin-1 (cleaved into Substance P)

                  ab133240

                  ab42295 

                  ab133029

                  CALCA

                  Calcitonin gene-related peptide 1 (CGRP)

                  ab81887

                  -

                  -


                  Research tools for inflammatory markers and growth factors

                  In the table below, you can find all the research tools that you need to trace key inflammatory markers and growth factors in neuropathic pain, including reliable recombinant monoclonal antibodies, quick SimpleStep ELISA kits, and high-quality bioactive proteins.

                  Did you know that our highly sensitive SimpleStep ELISA kits allow you to achieve reliable results within 90 minutes, with just one wash step?

                  Gene name

                  Target name

                  Species

                  Recombinant RabMAb antibodies

                  SimpleStep ELISA kits

                  Proteins

                  IL-1ß

                  Interleukin-1 beta

                  Human

                  ab216995


                  ab214025


                  ab259387


                  Mouse

                  ab234437

                  ab197742

                  ab259421

                  IL-6

                  Interleukin-6

                  Human

                  ab233706

                  ab178013

                  ab259381

                  Mouse

                  ab229381

                  ab222503

                  ab198572

                  TNFα

                  Tumor necrosis factor alpha

                  Human


                  ab215188

                  ab181421

                  ab259410

                  Mouse

                  -

                  ab259411

                  RELA

                  Transcription factor p65 (NFkB)

                  Human

                  ab32536


                  ab176663

                  ab114150

                  Mouse

                  -

                  -

                  BDNF

                  Brain-derived neurotrophic factor

                  Human


                  ab108319

                  ab212166

                  ab206642

                  Mouse

                  -

                  -

                  CXCL1

                  Growth-regulated alpha protein (C-X-C motif chemokine 1)

                  Human

                  ab206411

                  ab190805

                  ab92856

                  Mouse

                  -

                  ab216951

                  ab202817

                  CCL2

                  C-C motif chemokine 2 (MCP-1)

                  Human

                  ab214819

                  ab179886

                  ab269211

                  Mouse

                  -

                  ab208979

                  ab256241

                  CCL5

                  C-C motif chemokine 5 (RANTES)

                  Human

                  -

                  ab174446

                  ab269212

                  Mouse

                  -

                  -

                  ab243267


                  For multiplex quantification of protein biomarkers, our FirePlex®-96 immunoassay panels offer a fast, easy, and cost-effective tool to analyze large numbers of samples rapidly.

                  Recombinant monoclonal antibodies for key cellular and neuronal markers

                  Do you study the involvement of microglia or astrocytes in the pathogenesis of neuropathic pain? Get reliable and reproducible results with our recombinant monoclonal antibodies to key cellular and neuronal markers.

                  Cell type

                  Gene

                  Target

                  Recombinant RabMAb antibodies

                  Neurons

                  PRPH

                  Peripherin (predominant in the peripheral nervous system)

                  ab246502

                  NEFH

                  Neurofilament heavy polypeptide (NF200)

                  ab207176

                  TUBB3

                  Tubulin beta-3 chain (beta III Tubulin)

                  ab52623

                  RBFOX3

                  RNA binding protein fox-1 homolog 3 (NeuN)

                  ab177487

                  Macrophages

                  ITGAM

                  Integrin alpha-M (CD11b)

                  ab224805

                  ab184308

                  CD163

                  Scavenger receptor cysteine-rich type 1 protein M130 (CD163)

                  ab182422

                  ADGRE1

                  Adhesion G protein-coupled receptor E1 (F4/80)

                  ab254293

                  ab213200, ab111101

                  Microglia

                  IBA1

                  Calcium-binding adapter molecule 1

                  ab178846

                  MAPK11

                  Mitogen-activated protein kinase 11 (p38 MAPK)

                  ab137066

                  CCR2

                  C-C chemokine receptor type 2

                  ab254375

                  ab273050

                  Astrocytes

                  GFAP

                  Glial fibrillary acidic protein

                  ab68428

                  GJA1

                  Gap junction alpha-1 protein (Connexin-43, Cx43)

                  ab217676

                  MMP2

                  Matrix metalloproteinase-2

                  ab92536

                  MAPK8

                  Mitogen-activated protein kinase 8 (c-Jun N-terminal kinase 1, JNK1)

                  ab110724

                  References

                  1. Colloca, L., Ludman T, Bouhassira D, et al. Neuropathic pain. Nat Rev Dis Primers. 3:17002. (2017).
                  2. González-Ramírez, R., Chen, Y., Liedtke, W.B., et al. TRP Channels and Pain. In: Emir TLR, editor. Neurobiology of TRP Channels. Boca Raton (FL): CRC Press/Taylor & Francis; Chapter 8. (2017).
                  3. Woolf, C.J., Mannion, R.J. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet. 353:1959–64 (1999).
                  4. Zimmermann, M. Pathobiology of neuropathic pain. Eur J Pharmacol. 429:23–37 (2001).
                  5. Gilron, I., Watson, C.P.N., Cahill, C.M., Moulin, D.E. Neuropathic pain: a practical guide for the clinician. CMAJ. 175:265–75 (2006).
                  6. Kanai, Y. et al. Involvement of an increased spinal TRPV1 sensitization through its up-regulation in mechanical allodynia of CCI rats. Neuropharmacology, 49, 977–984 (2005).
                  7. Yamamoto, W. et al. Characterization of primary sensory neurons mediating static and dynamic allodynia in rat chronic constriction injury model. J Pharm Pharmacol, 60, 717–722 (2008).
                  8. Proudfoot, C.J. Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain. Curr Biol. 16, 1591-605(2006).
                  9. Dray, A. Neuropathic pain: emerging treatments, BJA: British Journal of Anaesthesia, 101, 48–58 (2008).
                  10. Hameed, S. Nav1.7 and Nav1.8: Role in the pathophysiology of pain. Mol Pain. 15:1744806919858801. (2019).
                  11. Hung, A.L., Lim, M., Doshi, T.L. Targeting cytokines for treatment of neuropathic pain. Scand J Pain. 17:287-293 (2017).


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