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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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                  • Inflammatory pain poster

                    ​​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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