Analgesic Development Software Is At The Core Of Producing Capsaicin Therapies

Designed to Cure

capsaicin is important in analgesic development
The chemical structure of capsaicin. Source: Wikipedia user Arrowsmaster.

Most know capsaicins as the family of compounds responsible for giving hot peppers their fire, but long bubbling interest in the capsaicins’ therapeutic potential is about to overflow, if researchers can pin down the family’s last pharmacological mysteries. In a review published in the Molecules journal, researchers from the National Leading Research Laboratory of South Korea claim that the capsaicin family’s analgesic, anti-inflammatory, anti-cancer and other benefits are so promising that the remaining questions about capsaicin-triggered signaling are too good to pass up.1 If researchers want to delve into drug development within one of the capsaicin family’s many potential applications, they’ll need a cutting edge information technology platform which can keep up with multidisciplinary data generation and cutting edge analysis.

What’s Hot About Capsaicin

It’s clear that mastering capsaicin’s mechanism of action will open therapeutic doors in the neurological space that practitioners have considered closed for years. But how can an overtly noxious chemical become therapeutic?

The answer lies in capsaicin’s unique dual action on sensory neurons. Capsaicin’s effect on sensory neurons is something that most people have experienced firsthand, but perhaps not appreciated at the cellular and molecular level. Upon capsaicin binding to the TRPV1 receptor on the external surfaces of sensory neurons, the neurons become sharply excited—sending the nociceptive “burning” signal—and then subsequently become heavily inhibited and unresponsive to stimuli.2 Importantly, this inhibition isn’t caused by follow-on inhibition downstream of the sensory neurons affected.3

The short duration of noxious stimulation can thus in turn reliably suppress overactive pain pathways, even if the pain isn’t caused by an external stimuli.4 This mechanism of action is broadly useful across many fields, as investigated deeply in the review’s summary of extant literature. In many physiological contexts of capsaicin therapies, patients wouldn’t even need to tolerate the noxious heat if the quantity of drug was titrated effectively. This is due to the additive magnitude of effect of the TRPV1 receptor ligation; the number of capsaicin molecules is directly linked to the subjectively perceived heat. The body of literature about TRPV1 ligands grows by the day, and new information about the TRPV1 receptor action itself is especially precious.

As it turns out, the TRPV1 receptor itself is a relatively recent discovery, as is its capsaicin binding scheme.5  As mentioned in the review, understanding capsaicin interaction with TRPV1 is only possible thanks to powerful software equipped with a mountain of molecular dynamics data. It’s a given that future research into capsaicin derivatives’ therapeutic potential will need to access and eventually contribute to this body of data before moving to the clinic.

Having easy access to a broad base of data is especially important in the context of capsaicin research: there are quite a few potential landmines that capsaicin researchers will need to avoid to make an effective therapy.

What’s Not So Hot About Capsaicin

There are a couple of caveats that researchers will need to stay abreast of while exploring capsaicin’s potential, namely awareness of noxious effects and caution regarding use case. These caveats aren’t related to facile difficulties like overdosing and overheating, but rather properties of capsaicin which aren’t fully concentration dependent.

First, there are instances of extreme cardiovascular stresses in some people when exposed to small amounts of capsaicin topically.6 This means that any capsaicin derived therapies would require extensive ethically questionable in vivo testing before moving into the clinic. There’s also the potential for hypersensitivity to capsaicin effects among humans, which capsaicin derivatives might also trigger.

Finally, there’s the spectre of cancer caused by repeated exposure to capsaicin, although the research is conflicting.7 8 Some studies found that capsaicin caused or accelerated tumor growth, whereas others found the opposite. Proponents of capsaicin as a novel therapeutic like the authors of the review have taken issue with the methodologies of some of the studies which found oncogenic effects in lab animals exposed to capsaicin. It’s highly likely that future drug development using capsaicin derivatives will need to develop high quality and realistic assays of oncogenicity from scratch. Meeting the high standards of regulators recently spooked by the hint of oncogenicity will be a data-heavy hurdle that researchers will need to be ready for.

Capsaicin’s Promise

The unanswered questions about capsaicin’s long term impact are unlikely to trouble researchers investigating it for most purposes, but for long term neurogenic pain relief—where capsaicin is very promising—answering will be necessary.

Handling capsaicin data and shaping it for drug development is a complex affair. Researchers will need to:

  • Collate molecular binding data for computational prediction of capsaicin derivatives’ binding affinity and magnitude of action
  • Collate TRPV1 pathway data
  • Collate sensory neuronal activation and inhibition pattern data across subjects and animal models
  • Track capsaicin derivative structures for screening
  • Track oncomarker data before and after capsaicin therapeutic exposure
  • Compare downstream efficacy of all animal model data with the substantial (and growing) body of human data
  • Share physiological impact data with subject matter experts
  • Assay neuronal tolerance to repeated capsaicin binding

Research groups will need a monster of a software platform to collect, collate, analyze, share, integrate, and act on all of this data. Because of the nature of how diverse the capsaicins’ impact can be, researchers will be pressed to integrate as much newly produced information as possible before planning experiments of their own, too. Standard small-scale or single-purpose laboratory information systems simply won’t be capable of keeping up with the scope and depth of investigations into capsaicin derived therapeutics.

Designed to Cure can enable your lab to fearlessly delve into the complex and multifactorial world of capsaicin research. Using Designed to Cure, developing novel capsaicin derivative therapies is possible. Contact us today to find out how we can help you break open the field of capsaicin neuronal therapies.

  1. “Harnessing the Therapeutic Potential of Capsaicin and Its Analogues in Pain and Other Diseases.” July 2016, http://www.mdpi.com/1420-3049/21/8/966/htm
  2. “The Two Faces of Capsaicin.” April 2011, http://cancerres.aacrjournals.org/content/71/8/2809.long#abstract-1
  3.  “The Capsaicin Receptor TRPV1 Is A Crucial Mediator Of The Noxious Effects Of Mustard Oil.” February 2011, https://www.ncbi.nlm.nih.gov/pubmed/21315593
  4. “Zucapsaicin For The Treatment Of Neuropathic Pain.” August 2014, http://www.tandfonline.com/doi/abs/10.1517/13543784.2014.956079?journalCode=ieid20
  5. “Structural Mechanism Underlying Capsaicin Binding and Activation of the TRPV1 Ion Channel.” May 2015, https://www.nature.com/nchembio/journal/v11/n7/full/nchembio.1835.html
  6. “Coronary Vasospasm and Acute Myocardial Infarction Induced By A Topical Capsaicin Patch.” 2009, https://www.journalagent.com/tkd/pdfs/TKDA_37_7_497_500.pdf
  7.  “Non-Mutagenicity of Capsaicin in Albino Mice.” 1988, http://www.sciencedirect.com/science/article/pii/0278691588900944?via%3Dihub
  8. “Carcinogenicity of Lifelong Administration of Capsaicin of Hot Pepper In Mice.” January 1992, http://europepmc.org/abstract/med/1627743