SUPERCHARGE
YOUR
UNDERSTANDING

OF SODIUM CHANNELS
IN ACUTE PAIN

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SUPERCHARGE
YOUR UNDERSTANDING

OF SODIUM CHANNELS
IN ACUTE PAIN

 

 

Dive even deeper into nociceptive pain signal transmission

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Explore how sodium channels Nav1.7, Nav1.8, and Nav1.9 transmit acute pain signals in the peripheral nervous system

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Acute
pain facts

 

 

 

  • Affects ~80 million people in the
    US each year1
  • Defined as pain lasting <3 months2
  • Occurs suddenly and is often caused by something specific, such as injury or surgery3

 

 

 

Understanding the underlying physiology of pain
signal transmission can play an important role in understanding and managing acute pain.

 

Understand the 
physiology of pain

Understand the 
physiology of pain

Understand the 
physiology of pain

Discover the 4 different stages of pain signal transmission:

01

Detection Nociceptors (pain-sensing neurons) detect noxious stimuli and initiate pain signals in the form of action potentials.4

02

Peripheral transmission These action potentials travel through the peripheral nervous system (PNS).5

03

Central transmission These action potentials propagate to the central nervous system (CNS), traveling up the spinal cord toward the brain.6

04

Perception These action potentials are interpreted by different regions of the brain where pain is perceived.7

NaV Open State: Generation of Action Potentials5,8,9

NaV Open State: Generation of Action Potentials5,8,9

NaV Open State: Generation of Action Potentials5,8,9

NaV Closed State: No Generation of Action Potentials8

NaV Closed State: No Generation of Action Potentials8

NaV Closed State: No Generation of Action Potentials8

Sodium channels play a pivotal role in pain signal transmission7

Sodium channels play a pivotal role in pain signal transmission7

Sodium channels play a pivotal
role in pain signal transmission7

The opening of voltage-gated sodium channels (NaVs) within nociceptors in response to external stimuli allows for the movement of sodium ions into the neuron, which initiates action potentials.10

Opening of the NaVs in one region of the neuron causes nearby NaVs to also open and allows pain signal transmission along the peripheral sensory neuron.8

NaVs are crucial to action potential propagation and pain signal transmission from the PNS to the CNS.7

See how pain is
transmitted through NaVs

See how pain is
transmitted through NaVs

See how pain is
transmitted through NaVs

Nav1.7, Nav1.8, and Nav1.9 are expressed in peripheral nociceptive neurons. Their activity is intrinsic to propagating pain signals and may help us to better understand pain.7,11

Development of
pain pharmaceutical
treatments

Development of pain pharmaceutical treatments

Development
of pain pharmaceutical treatments

 

 

 

  • Although current therapies are effective for reducing acute pain in different clinical situations,17 they also have limitations due to side effects, contraindications,18,19 and/or abuse potential20
  • This may result in inadequate pain treatment and further underscores the urgency for therapeutic alternatives
Despite the significant prevalence of patients who experience pain and its known complications, there still remains an unmet need for pharmaceutical innovation.20,27

Despite the significant prevalence of patients who experience pain and its known complications, there still remains an unmet need for pharmaceutical innovation.20,27

Despite the significant prevalence of patients who experience pain and its known complications, there still remains an unmet need for pharmaceutical innovation.20,27

There are 9 sodium channel subtypes, and each is expressed differently throughout the body.

Since the 1990s, Vertex has been committed to understanding pain signal transmission.

There are 9 sodium channel subtypes, and each is expressed differently throughout the body.

Since the 1990s, Vertex has been committed to understanding pain signal transmission.

There are 9 sodium
channel subtypes,
and each is
expressed
differently throughout
the body.

Since the 1990s,
Vertex has been
committed to
understanding pain
signal transmission.

References

1. Lopez A, Jones J, Menzie AM, Peta S, Ippolito A, Rubin J. An evaluation of the prevalence of acute and chronic pain medication use in the United States: a real-world database analysis. Presented at: ASRA Annual Pain Medicine Meeting; November 10-11, 2023; New Orleans, LA. 2. Banerjee S, Argáez C. Multidisciplinary Treatment Programs for Patients With Acute Or Subacute Pain: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines. Canadian Agency for Drugs and Technologies in Health; 2019. Accessed May 1, 2024. https://www.ncbi.nlm.nih.gov/books/NBK546002/ 3. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC clinical practice guideline for prescribing opioids for pain United States, 2022. MMWR Recomm Rep. 2022;71(3):1-95. doi:10.15585/mmwr.rr7103a1 4. Garland EL. Pain processing in the human nervous system: a selective review of nociceptive and biobehavioral pathways. Prim Care. 2012;39(3):561-571. doi:10.1016/j.pop.2012.06.01 5. de Lera Ruiz M, Kraus RL. Voltage-gated sodium channels: structure, function, pharmacology, and clinical indications. J Med Chem. 2015;58(18):7093-7118. doi:10.1021/jm501981g 6. Waxman SG. Targeting a peripheral sodium channel to treat pain. N Engl J Med. 2023;389(5):466-469. doi:10.1056/NEJMe2305708 7. England S. Voltage-gated sodium channels: the search for subtype-selective analgesics. Expert Opin Investig Drugs. 2008;17(12):1849-1864. doi:10.1517/13543780802514559 8. Grider MH, Jessu R, Kabir R. Physiology, Action Potential. StatPearls Publishing; 2022. Accessed May 1, 2024. https://www.ncbi.nlm.nih.gov/books/NBK538143/ 9. Goodwin G, McMahon SB. The physiological function of different voltage-gated sodium channels in pain. Nat Rev Neurosci. 2021;22(5):263-274. doi:10.1038/s41583-021-00444-w 10. Catterall WA. Voltage-gated sodium channels at 60: structure, function and pathophysiology. J Physiol. 2012;590(11):2577-2589. doi:10.1113/jphysiol.2011.224204 11. Hameed S. Nav1.7 and Nav1.8: role in the pathophysiology of pain. Mol Pain. 2019;15:1744806919858801. doi:10.1177/1744806919858801 12. Wang J, Ou SW, Wang YJ. Distribution and function of voltage-gated sodium channels in the nervous system. Channels (Austin). 2017;11(6):534-554. doi:10.1080/19336950.2017.1380758 13. Bennet DL, Clark AJ, Huang J, Waxman SG, Dib-Hajj SD. The role of voltage-gated sodium channels in pain signaling. Physiol Rev. 2019;99(2):1079-1151. doi:10.1152/physrev.00052.2017 14. Yu FH, Catterall WA. Overview of the voltage-gated sodium channel family. Genome Biol. 2003;4(3):207. doi:10.1186/gb-2003-4-3-207 15. Faber CG, Lauria G, Merkies IS, et al. Gain-of-function Nav1.8 mutations in painful neuropathy. Proc Natl Acad Sci USA. 2012;109(47):19444-19449. doi:10.1073/pnas.1216080109 16. Emery EC, Luiz AP, Wood JN. Nav1.7 and other voltage-gated sodium channels as drug targets for pain relief. Expert Opin Ther Targets. 2016;20(8):975-983. doi:10.1517/14728222.2016.1162295 17. Hyland SJ, Brockhaus KK, Vincent WR, et al. Perioperative pain management and opioid stewardship: a practical guide. Healthcare (Basel). 2021;9(3):333. doi:10.3390/healthcare9030333 18. Ghlichloo I, Garriets V. Nonsteroidal Anti-inflammatory Drugs (NSAIDs). StatPearls Publishing; 2023. Accessed May 1, 2024. https://ncbi.nlm.nih.gov/books/NBK547742/ 19. Amaechi O, Huffman MM, Featherstone K. Pharmacology therapy for acute pain. Am Fam Physician. 2021;104(1):63-72. 20. Sinatra R. Causes and consequences of inadequate management of acute pain. Pain Med. 2010;11(12):1859-1871. doi:10.1111/j.1526-4637.2010.00983.x 21. Zhou S, Huang G, Chen G. Synthesis and biological activities of local anesthetics. RSC Adv. 2019;9(70):41173-41191. doi:10.1039/c9ra09287k 22. El-Bogdadi D. Impact of combinations of non-steroidal anti-inflammatory drugs. Accessed May 1, 2024. https://arapc.com/nsaid-story/ 23. Beckwith MC, Fox ER, Chandramouli J. Removing meperidine from the health-system formulary--frequently asked questions. J Pain Palliat Care Pharmacother. 2002;16(3):45-59. doi:10.1080/j354v16n03_05 24. Woodcock J. Re: Selection of Acetaminophen for Consideration for Listing by the Carcinogen Identification Committee. U.S. Food and Drug Administration, Center for Drug Evaluation and Research; 2019. Accessed May 1, 2024. https://oehha.ca.gov/media/dockets/19653/19710-u.s._food_and_drug_administration_fda/fda_comments_notice_of_availability_of_hazard_identification_materials_for_acetaminophen_1142019.pdf 25. Wiffen PJ, Derry S, Moore RA, et al. Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews. Cochrane Database Syst Rev. 2013;2013(11):CD010567. doi:10.1002/14651858.CD010567.pub2 26. Gong L, Thorn CF, Bertagnolli MM, Grosser T, Altman RB, Klein TE. Celecoxib pathways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics. 2012;22(4):310-318. doi:10.1097/FPC.0b013e32834f94cb 27. Thomas D. Pain and addiction therapeutics. The State of Innovation in Highly Prevalent Chronic Diseases. Accessed May 1, 2024. https://go.bio.org/rs/490-EHZ-999/images/BIO_HPCP_Series-Pain_Addiction_2018-02-08.pdf