Neuropathic pain: overview and research tools

​​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 pain^3,4. 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 pain^6,7, 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 Na_V1.3, Na_V1.7, Na_V1.8) 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 unclear^9,10.

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. 

Biochemicals targeting ion channels

​​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.

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?

Recombinant monoclonal antibodies for key cellular and neuronal markers

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. Na_v1.7 and Na_v1.8: 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).