The Disease

Nociceptive pain is pain that originates because of stimulation of nerves located in the tissues in our body.  Let’s assume we cut some skin off our finger.  When this happens, receptors at the ends of the nerves in the skin of our finger are stimulated; this causes an “action potential” in the nerve which transfers the information along that nerve; that nerve will transfer the information to another nerve or nerves until it gets to the spinal cord; the spinal cord transfers this information up to our brain stem; the brain stem distributes this information to many different parts of the brain; each part “reports their analysis of this information” back to the brain stem;  the brain stem sends a “report” to the pain center in our brain, and our pain center analyzes this information and decides whether or not to let you know if your finger hurts.  I am sure many of you have cut your finger at some point and didn’t feel pain until you saw that you had cut your finger.  Until you saw the cut, your brain had decided that the information being sent to it from your nerves was false information.  When you saw the cut, your brain got more information from a different source, added this information the report, the pain center re-analyzed the situation and “changed its mind” and told you “your finger hurts”; and told you exactly where it hurt.  

As you can see from the above, lots of different kinds of nerves are involved in nociceptive pain, but it always starts by stimulation of receptors on the ends of the nerves.   Nociceptive pain can be caused by: mechanical forces (pinching, cutting, stretching, etc.), heat and cold, chemical irritation, and inflammation.  In all cases, the of these receptors are located on the ends of nerves and are stimulated via transient receptor potential (TRP) channels that sense and detect and damage occurring in the tissue.

Research Findings

As stated above, nociceptive pain occurs because of stimulation of transient receptor potential (TRP) channels on the ends nerves that lie in the tissues of our body.1  Only three of the six TRP sub-families, TRPV, TRPA, and TRPM, have been have been identified as being responsible for nociceptive pain.1 In each of these subfamilies only six specific channels (TRPV1,TRPV2,TRPV3, TRPV4, TRPA1 and TRPM8) are found to in nociceptive nerves.2,3  Activation of these nociceptive TRP channels by specific noxious and/or pain-producing stimuli serves as the principal mode of detection/transduction of pain under physiological and pathophysiological conditions.1  Some nerves will have only one specific TRP channel which allows them only to respond to the stimuli that activate that specific channel, i.e. certain nerves have only TRPM8 allowing them to respond only to pressure and shearing pain.1  However, most nerves have multiple TRPV channels allowing that nerve to respond to multiple types of pain.1  TRPV1 and TPRA1 are often found together on nerves and both activated in many noxious situations including inflammatory pain, visceral pain, migraines, etc.1    Nociceptive TRP channels are membrane proteins, and most are found in the neuronal/cell membrane.4 However, a significant number are present in intracellular organelle membranes of the nerves and these channels will migrate to the cell membrane when the cell undergoes significant and/or persistent injury or inflammation, increasing the intensity of the “felt pain” and leading to hyperalgesia (see neuropathic pain).1,5-9  Often inflammation in the tissue begins after the inciting stimulus.  This causes the release of various chemicals which cause vasodilation (the source of the redness and swelling associated with inflammation) and sensitization of the TRP channels leading to hyperalgesia (minor touching of the damaged area that normally doesn’t cause pain but now does).1,5-8,10  All of these changes result in constant activation and mobilization of the TRP’s which is responsible for the feeling of constant and increasing pain, even though the initial stimulus that caused the pain is no longer present.

CBD desensitizes TRPV1-4 and TRPA1 receptors such that they are unable to generate an action potential, causing the nerves to be unable to send “pain” messages to the spinal cord.11,12  In addition, CBD inhibits TRPM8 receptors which does the same thing.13 However, other cannabinoids including cannabinol (CBN), cannabichromene (CBC), cannabigerol (CBG), and THC also desensitize these receptors and inhibit the nerves from depolarizing and sending “pain” messages to the spinal cord.11  Often TRP channels are linked with other known cannabinoid receptors, i.e., CB2, 5-HT1A, etc.11  Cannabinoids binding to these receptors interact with their associated TRP channels causing desensitization and prohibition of generating nerve impulses.11

Numerous studies have been performed using chemically produced blockers of TRP’s and several have found them to be somewhat effective in the relief of specific types of nociceptive pain, however, because they all have been specific blockers of only one type of TRP (example: blocks only TRPV1 and not any others) and, in most painful situations, multiple TRP’s are being stimulated, they have not been universally useful in nociceptive pain.  However, because of its ability to block all the TRP’s associated with nociceptive pain, CBD-enhanced full spectrum hemp oil should be more effective in preventing nociceptive pain than chemically produced TRP blockers.  In addition, because it contains many other cannabinoids known to also block TRP’s, CBD-enriched hemp oil should be better at controlling nociceptive pain than CBD alone.

Bottom Line

Nociceptive pain is the most common type of pain and is caused by physical damage or potential damage to the body.  CBD-enriched hemp oil containing multiple other cannabinoids has great potential in being able to block sensory nerves from generating nerve impulses resulting in the elimination of nociceptive pain.  No studies of CBD-enriched hemp oil in nociceptive pain have been reported and, at this time, the FDA does not approve the use of CBD products for nociceptive pain.



  1. Mickle AD, etal. Nociceptive TRP channels: Sensory detectors and transducers in multiple pain pathologies. Pharmaceuticals 2016;9:72
  2. Marwaha L, etal. TRP channels: potential drug target for neuropathic pain.  2016 Dec;24(6):305-317.
  3. Sałat K, etal. Transient receptor potential channels – emerging novel drug targets for the treatment of pain.  Curr Med Chem. 2013;20(11):1409-36.
  4. Ferrandiz-Huertas C, etal. Trafficking of thermo-TRP channels. Membranes 2014;4:525–64.
  5. Mickle A.D, etal. Induction of thermal and mechanical hypersensitivity by parathyroid hormone-related peptide through upregulation of TRPV1 function and trafficking. Pain 2015;156:1620–36.
  6. Zhang X, etal. NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. EMBO J. 2005;24:4211–23.
  7. Schmidt M, etal. Nociceptive signals induce trafficking of TRPA1 to the plasma membrane. Neuron 2009;64:498–509.
  8. Meng J, etal. TNF alpha induces co-trafficking of TRPV1/TRPA1 in VAMP1-containing vesicles to the plasmalemma via Munc18-1/syntaxin1/SNAP-25 mediated fusion. Sci. Rep. 2016;6:21226.
  9. Bandell, M, etal. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 2004;41:849–57.
  10. Julius D. TRP channels and pain. Annu Rev Cell Dev Biol. 2013;29:355-84.
  11. Akopian AN, etal. Role of ionotropic cannabinoid receptors in peripheral antinociception and antihyperalgesia.  Trends Pharmacol Sci 2009;30(2):79-84.
  12. Iannotti FA, etal. Non-psychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability. ACS Chem Neurosci. 2014;5(11):1131-41.
  13. De Petrocellis L, etal. Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. J Pharmacol Exp Ther. 2008 Jun;325(3):1007-15.




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