Pain

International Association for the Study of Pain (IASP): “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.“

  • What is Pain?
  • Pain & cannabinoids
  • Text references, literature discussion
    & clinical trials

What is Pain?

Definition
A broadly recognized definition of pain is proposed by the International Association for the Study of Pain (IASP): “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.“1

Symptoms
Symptoms of pain can differ between people. Given the subjectiveness of pain, the symptoms vary greatly but common non-verbal symptoms may be:2

  • Distortion of facial grimace
  • Whimpering, groaning, and moaning
  • Constant movement e.g. restlessness and distress
  • Uneasy and tense appearance e.g. kicking
  • Actively avoiding to physically touch the area of pain

In addition, the symptoms of pain may be described as a feeling of pinching, soring, stinging, or throbbing in either a local area or a general feeling in the entire body. The range of pain is very broad. It can appear acute, consistent, or chronic and it can vary in magnitude depending on the pain tolerance which differs between people.3

Cause – How underlying aspects may interfere with pain perception?

The pain experienced by individuals must always be accepted and respected as it is perceived.
However, it is important to understand the role of underlying factors that may influence pain perception including but not limited to:4

  • The individual’s concept of pain and how it may appear
  • Nociception. and pain must not be mistaken, as pain is not limited to an unpleasant activity in the sensory nervous system
  • Even if the pain may be perceived as a local unpleasantness, it can also affect other aspects of life greatly
  • Pain can be expressed in several ways that are not verbal meaning that pain can be felt without the ability to express it
  • Cannabinoids
  • Cannabinoid receptors
  • Endocannabinoids
  • CBD
  • CBG
  • THC
  • CB1
  • CB2
  • GPR55
  • PPARα
  • TRPA1
  • TRPM8
  • TRPV1
  • TRPV2
  • TRPV3
  • TRPV4
  • α2r
  • GlyR
  • Anandamide
  • PEA
  • 2AG
  • Terpenes
  • Strains
  • Enzymes
  • Metabolites
  • Caryophyllene
  • Eugenol
  • Myrcene
  • Pinene
  • Limonene
  • Linalool

Strains

  • FAAH
  • MAGL
  • DAGL

Metabolites

The connection between Pain
& cannabinoids

Pain

Evidence supports the role of endocannabinoids in pain modulation as the cannabinoid receptor CB1 is present in the nervous system involved in the modulation of nociception. Therefore, cannabinoids may provide a promising treatment for conditions associated with pain.5

Preclinical- and clinical data propose that the cannabinoids THC, CBD, and to some extent CBG may be therapeutic in the treatment of pain. However, more studies need to be conducted to understand the full potential of cannabinoids in pain management.6

Note: If you have any further information relevant to the connection between Pain and cannabinoids, or find any of the information inaccurate, outdated, or incomplete please contact us here.

Text references, literature discussion
& clinical trials

  • Text references
  • Literature discussion
  • Clinical trials
Review

Pain, cancer, neurodegenerative diseases, ischemic injuries, inflammation, anxiety, nausea, and drug-withdrawal symptoms can possibly be treated by MAGL inhibitors, which showed potential therapeutic action (Chen et al., 2012; Kohnz & Nomura, 2014; Mulvihill & Nomura, 2013).

The analgesic action of paracetamol was shown to be prevented through blocking CB1, proposing that CB1 is needed for analgesia (Bertolini et al., 2006).

Similarly, the breakdown/hydrolysis of anandamide was shown to be blocked by ibuprofen, which may contribute to the analgesic properties of ibuprofen (Fowler et al., 1999).

In mice, the analgesic effect of THC was found to be potentiated by inhibition of opioid-degrading enzymes, proposing that there is a synergistic effect between the opioid- and endocannabinoid systems in pain management (Reche et al., 1998).

In a rat model, muscle pain was shown to be inhibited by THC through activation of CB1 (Bagüés et al., 2014).

Several synthetic CB2 agonists have obtained a patent due to their analgesic effects, showing that CB2 plays an important role in pain management (Murineddu et al., 2012).

TRP receptors are involved in pain sensation.

It was shown that there is an interaction between TRPs and cannabinoids (endo and phytocannabinoids) with varying affinities (De Petrocellis et al., 2011, 2012). This means that TRPs can be excellent targets and plant cannabinoids excellent substrates to manage pain.

In patients with Chronic Widespread pain, a decrease in pain intensity was connected to high levels of PEA via the PPARα receptor (Ghafouri et al., 2013).

In rats, algesia can be reduced through blocking GPR55 signaling, proposing that GPR55 is a target to control pain (Deliu et al., 2015).

In vivo studies aimed to evaluate nasal and transdermal permeation using rats and guinea pigs, respectively. Intranasal delivery of CBD showed a bioavailability of 34-46% with CBD being absorbed within 10 minutes. Polyethylene glycol formulation in rats showed a bioavailability of 100% and the use of enhancers did not improve bioavailability. Transdermal gel application in guinea pigs showed that the steady-state plasma concentration of CBD was sufficiently high for this administration route for CBD to be considered beneficial for treating chronic pain. Furthermore, it was demonstrated that with the use of enhancers, the steady-state concentration of CBD was increased by 3.7-fold. This shows that CBD could be successfully administered intranasally or transdermally (Paudel et al., 2010).

References

Paudel, Kalpana S., et al. “Cannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers.” Drug development and industrial pharmacy 36.9 (2010): 1088-1097.

Clinical trials

Many clinical trials have assessed the effectiveness of cannabinoids to inhibit pain with different results.

It was shown that the most effective effect can be produced by THC and CBD mixture.
Moreover, cannabinoids may be more effective in inhibiting chronic pain than acute pain.

Finally, cannabinoid combination with other pain medications such as opioids, paracetamol, ibuprofen can be used to exhibit a stronger effect to relieve pain.

Post-operative pain was shown to be reduced by oral cannabis extract (Holdcroft et al., 2006).

A randomized, double-blinded, placebo-controlled trial included 27 people with chronic pain to assess the pharmacokinetics, analgesic properties, cognitive performance, and safety effects of cannabis inhaler (THC: 0.5mg, 1mg). It was found that pain intensity was significantly reduced by both doses compared with the control group, highlighting that THC exhibits analgesic effects. Mostly mild adverse events were found and non-severe. Also, there was no evidence that cognitive performance was consistently impaired (Almog et al., 2020).

References

Almog, Shlomo, et al. “The pharmacokinetics, efficacy, and safety of a novel selective‐dose cannabis inhaler in patients with chronic pain: A randomized, double‐blinded, placebo‐controlled trial.” European Journal of Pain 24.8 (2020): 1505-1516.

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