Chronic pain conditions
neurogenic or neuropathic pain
Life with chronic pain in Denmark
In Denmark, chronic pain is a significant health problem. According to figures from the Danish Health Authority, around 1.6 million Danes experienced chronic pain in 2017. The prevalence of chronic pain typically increases with age, with older people experiencing pain more often than younger people.
Chronic pain is a complex and challenging reality for many Danes. The daily struggle to manage this pain affects not only physical well-being but also mental and emotional well-being. This post will explore the daily lives of those living with chronic pain in Denmark and look at the approved medications used to manage this painful condition.
Daily life with chronic pain
Living with chronic pain in the UK often involves a constant struggle to maintain an acceptable quality of life. People suffering from chronic pain often experience:
Physical challenge: Basic daily activities, such as walking, sitting, or even sleeping, can become formidable tasks for those with chronic pain. This affects not only mobility but also the ability to perform daily tasks.
Psychological impact: Chronic pain has a significant impact on mental health. Feelings of frustration, isolation and hopelessness are common. Many also experience depression and anxiety as a result of the constant pain and challenges they face.
Social challenges: Chronic pain can lead to social isolation as it can be difficult to attend social events or maintain social relationships. This further contributes to the feeling of being cut off from society.
Being a chronic pain patient in Denmark involves a complex journey filled with physical, mental and social challenges. Although there are approved medications and treatment options available, there is still a need for improved understanding and support from society and the healthcare system to ease the burden of those living with chronic pain. A holistic approach that combines medical treatment, physiotherapy and psychological support can be crucial to improving the quality of life for these individuals.
Despite the availability of these treatment options, many chronic pain patients face challenges in the Danish healthcare system. These include:
Waiting times: Long waiting times at specialised pain clinics can delay access to necessary treatment.
Lack of understanding: Stigmatization and lack of understanding of chronic pain in society and among healthcare professionals can lead to frustration and isolation for patients.
Fragmented treatment: Some patients find that treatment is fragmented and doesn't consider their needs, indicating the need for more holistic approaches.
Different types of chronic pain conditions
Pain that persists for more than 3-6 months is considered chronic, especially when traditional treatment methods have not been sufficiently effective. Chronic pain can occur as a result of[1]:
Nociceptive pain
Damage to joints, tissues, muscles and bones: The pain is perceived as deep, dull (tingling) or piercing and may resemble a toothache. Usually, the pain disappears as the injury heals, but in some cases, it can develop into chronic pain. These are called nociceptive pain as they relate to nociceptors, nerve endings that detect tissue damage.
Neuropathic pain
Disease or damage to the nerves (nerve fibres or nerve roots), brain or spinal cord: The pain can be perceived as burning and stinging, similar to sunburn or tingling like when the leg is asleep. Stabbing or stabbing pain can also occur, like electric shocks. This pain condition can occur in diseases such as diabetes, shingles, poor circulation, blood clots or bleeding in the brain, herniated discs, amputation (in the form of phantom limb pain) or after other surgeries. This pain is referred to as neuropathic or nerve pain.
Sensitisation states
A pain condition with no apparent cause in prior bodily injury: This type of pain occurs due to changes in the pain sufferer's ability to detect pain. Although the body is not necessarily damaged, the brain perceives specific signals as pain. The mechanism that leads to this type of pain is called "central sensitisation", which means that the patient develops increased sensitivity of the nerve cells in the spinal cord and brain. The nervous system, therefore, reacts more quickly to stimuli that are not necessarily painful. These pains are referred to as sensitisation states and can occur in conditions such as fibromyalgia or as a result of Whiplash Associated Disorder (WAD), vulvodynia, etc.
The patient often experiences a pain condition that combines the three main types mentioned. It is up to the multidisciplinary treatment team to identify the specific pain types and the psychological and social factors involved in the patient's overall pain experience. Only then is it possible to design a treatment program, which can be either mono-disciplinary (includes doctors and nurses) or multidisciplinary (includes doctors, nurses, psychologists and physiotherapists). Overall, understanding these pain types is complex and treatment strategies should be individually tailored based on the patient's specific condition, causes and response to treatment. Further research is essential to improve our understanding of these pain conditions and develop more effective treatment methods.
An overview of different pain medications
Pain medications fall into several categories and subcategories. Firstly, medicine distinguishes between "non-opioids" and "opioids"[2].
Non-opioids include:
Paracetamol: For mild to moderate pain, moderate to severe pain (in addition to opioids) and temporary fever reduction.
NSAIDs (non-steroidal anti-inflammatory drugs, e.g. ibuprofen and diclofenac): For mild to moderate pain, pain associated with inflammation and temporary fever reduction.
Opioids contain opium-like active ingredients, such as those found in the dried milky white sap of the poppy plant. The main active and naturally occurring components - known as opiates - are morphine, codeine and thebaine[3]. Synthetic opioids act on both the peripheral and central nervous system by binding to opioid receptors[2]. It is also through these receptors that the side effects, some of them severe, are triggered. Opioids are divided into 'weak' and 'strong' opioid analgesics. The weak opioids include painkillers such as tilidine and tramadol, as well as codeine, which is used as a cough suppressant. The best-known active ingredients in strong opioids include:
Fentanyl
Hydromorphone
Levomethadone
Morphine
Oxycodone
Piritramide
Remifentanil
Sufentanil
Which painkillers are appropriate for the treatment of chronic pain?
Adequate pain management is as important as it is complex. Treating physicians must include many aspects in their decisions, constantly questioning their treatment methods and adjusting them if necessary. It's important to consider all of the patient's diseases and conditions. Interactions with other medications and the patient's personal circumstances also play a significant role in choosing the appropriate medication. Therapy is highly individualised.
In the long-term treatment of mild to moderate chronic pain, paracetamol is often the analgesic of choice, as it is a safe and effective drug when used correctly. However, if the drug is taken over a more extended period, unwanted side effects can occur. The main concerns are bleeding in the digestive tract and high blood pressure (see below). NSAIDs can also be used to treat chronic pain but can cause numerous unwanted side effects. Risks exist, especially for the cardiovascular system, digestive tract and kidneys. Therefore, regular monitoring is strongly recommended for chronic patients who take NSAIDs regularly.
Opioids are commonly used to treat severe chronic pain. However, the use of opioids is controversial due to the risk of addiction, tolerance and severe side effects[2].
The side effects of opioids are extensive. They can include[2,4]:
Constipation
Nausea and vomiting
Development of tolerance
Respiratory depression
Inhibition of the cough reflex
Pupillary changes
Drowsiness and dizziness
Headaches
Itching
Loss of appetite
Depression/euphoria
Stiffness in skeletal muscles
Physical dependence
To avoid habituation, it is recommended to vary with different opioids. To prevent withdrawal symptoms after long-term use, the medication should be gradually phased out.
Other treatment options: What else can help patients?
Some medicines that were not developed as painkillers in the strict sense of the word still have analgesic properties. In some cases, doctors decide to prescribe such drugs further. This happens mainly when one or more indications correspond to the actual scope of use. The so-called co-analgesics include:
Antidepressants: The drugs used to treat depression block the reuptake of certain neurotransmitters in descending pain-inhibiting nerve pathways and thus improve pain modulation. The analgesic effects of antidepressants are used mainly for neuropathic pain conditions, fibromyalgia, chronic musculoskeletal pain, migraines and tension headaches[2].
Antiepileptic drugs: They are used to treat epilepsy as they reduce the release of neurotransmitters or the activity of neurons. Therefore, it is used for nerve pain and fibromyalgia[2].
Glucocorticoids: These hormones, which include cortisone, have an anti-inflammatory effect, thus inhibiting the development of inflammation and the associated perception of pain. In addition, they eliminate fluid accumulation in the tissue (oedema) and thus relieve pressure on pain-sensitive structures[2].
Regulators of calcium metabolism[5,6,7,8]: Calcitonin and bisphosphonates can be used for pain relief in spinal fractures, bone tumours, osteoporosis and neuropathic pain. Calcitonin has also been shown to have analgesic effects in phantom limb pain.
In addition to drug therapy, psychological support for pain patients is also crucial. Persistent pain takes a toll on the psyche of those affected. Their living conditions often change: some pain patients can no longer carry out their daily life, including work, social contacts and hobbies. Exchanges with other sufferers can also help them accept the new life situation - support groups provide the necessary space.
Nutritional counselling and dietary changes can also help patients. For example, there are indications that specific diets can be helpful in addition to anti-inflammatory pain therapy with medication in treating rheumatoid arthritis[9].
The issue of exercise also plays a role in chronic pain. Depending on the clinical picture, practising sports adapted to the health condition is considered health-promoting. Patients should always discuss what type of sport is considered appropriate at what time with the person providing medical support for pain therapy.
Pain patients may also benefit from physical and occupational therapy in this context.
How does medical cannabis reduce pain?
Experts believe that the effect of cannabis on pain can be explained by cannabinoids such as THC and CBD interacting with the body's endocannabinoid system[10].
The endocannabinoid system (ECS) is a regulatory system consisting of receptors for endogenous cannabinoids. These so-called endocannabinoids can activate the receptors as needed and affect specific processes. These processes include pain perception, emotion regulation, sleep and the immune system.
In addition, the active substances in the cannabis plant (phytocannabinoids) can also bind to these receptors, activating them and causing similar effects. In total, the cannabis plant contains more than 100 cannabinoids, only a few of which have been studied so far. THC and CBD are the most widespread and best-studied phytocannabinoids.
The primary receptors are cannabinoid receptor 1 (CB1) and 2 (CB2). Both are thought to have analgesic effects when activated. CB1 is commonly found in the central nervous system, while CB2 is frequently found in immune cells. Both receptors are distributed throughout the body[10].
Medical cannabis is not a panacea - and should, therefore, also be used with caution. Most prescriptions for medical cannabis are for chronic pain, and scientific studies support the effect on neuropathic pain in particular. It is somewhat questionable whether cannabis is effective for acute pain[10,12,13,14].
THC is considered the prominent analgesic cannabinoid, but CBD also contributes to the analgesic effect. Furthermore, the combination of these two cannabinoids seems to enhance the positive effects while reducing the unwanted side effects of THC. One of the mechanisms involved in the analgesic development of cannabinoids is a reduction in the release of neurotransmitters by neurons, which alters pain sensation [15].
Studies show that cannabis is not a classic analgesic but instead helps patients perceive the pain as less disturbing[16]. The pain does not disappear but is perceived as less unpleasant with cannabinoid treatment.
How is medical cannabis used for chronic pain indications?
Cannabis can be a valuable aid in pain management. Cannabinoids can be prescribed as an adjunct to common painkillers, such as opioids. Patients who do not get sufficient relief from conventional treatments can benefit from the possibilities of supplementary cannabinoid therapy.
For people suffering from the sometimes very unpleasant side effects of opioids, pain management with cannabinoids can also be beneficial[17]. Optimally, the dosage of opioids can be reduced due to the altered pain perception, which in turn can reduce side effects and the risk of opioid addiction.
Other benefits of medical cannabis
Several studies also suggest that phytocannabinoids can reduce the side effects of strong painkillers and secondary symptoms of chronic conditions:
Nausea and vomiting is a common side effect of opioid therapy. Studies of cannabis treatment during chemotherapy have shown that cannabis can alleviate nausea and vomiting[13].
Some patients suffer from loss of appetite and weight loss due to prolonged severe pain. Reduced appetite is also a common side effect of opioid pain management. Cannabis has been shown to stimulate appetite[13].
Many pain patients suffer from depression as a result of their chronic pain. According to a German study, 2.8% of cannabis medication is prescribed for depression[18].
Sleep disturbances are not uncommon among people with chronic pain and are an additional burden. Research groups point to the possible sleep-promoting effect of medicinal cannabis[19].
Which cannabis preparations for pain can be prescribed by a doctor?
Medicines containing substances found in the cannabis plant are called cannabis-based medicines, whereas plant parts or extracts of plant parts from the cannabis plant are called medicinal cannabis. A doctor can prescribe cannabis-based medicine and has been able to do so for many years. Doctors can now also prescribe medicinal cannabis but are not obliged to do so, even if the patient meets all the conditions for receiving it.
Cannabis preparations under the medicinal cannabis pilot program
Medicinal cannabis is plant parts or extracts from the cannabis plant. Medicinal cannabis is not registered anywhere in the world as an authorised medicinal product[20]. Medicinal cannabis is covered by the frame that entered into force on 1 January 2018 and was extended for another four years in 2022. All cannabis products to be included in the medicinal cannabis pilot programme must be included on a list published by the Danish Medicines Agency. This makes it possible for everyone to see which cannabis products are legally available for prescription by doctors and dispensed by pharmacies in Denmark. See the list of cannabis products included in the pilot program here.
The medical cannabis group includes the following cannabis products:
Herbal tea/inhalation vapour
THC cannabis flower
Balanced (THC and CBD) cannabis flower
Oral cannabis oils
CBD oil
THC oil
Cannabis preparations under the magistral scheme with cannabis-based medicines
Cannabis-based medicines, on the other hand, are medicines that meet the strict requirements set by the health authorities for the manufacturer. For many years, doctors have been able to prescribe cannabis-based medicines to patients. Cannabis-based medicines are not covered by the bill.11 Cannabis-based medicines are ready-to-use capsules or oil.
Cannabis-based medicine is produced at Glostrup Apotek, where oral drops/capsules are made:
THC oil
CBD oil
Balanced (THC and CBD) oil
Approved medicines
Have been through the official drug approval process and have therefore been tested in controlled laboratory trials, animal studies and by human subjects. The companies have submitted all data from the trials to the authorities, who have assessed that the medicine’s benefits outweigh the risk of side effects.
Sativex is an oral spray based on cannabis extracts containing the substances THC (dronabinol) and CBD (cannabidiol). Sativex is approved for symptom relief in adult patients with moderate to severe spasticity due to multiple sclerosis (MS) who have not responded adequately to other antispastic medications and who show clinically significant improvement in spasticity-related symptoms during an initial trial of treatment. Specialists in neurology and neuro medicine can prescribe Sativex.
Epidyolex is an oral solution containing CBD from the cannabis plant. Epidyolex is approved in the EU for the treatment of the epilepsy disorders Dravet Syndrome and Lennox-Gastaut Syndrome. The approval of Epidyolex only covers the two indications for which the company has applied for permission and only in combination with another approved medicine for treating epilepsy, clobazam. Specialists in neurology and paediatrics can prescribe Epidyolex.
Non-authorized medicines (dispensing authorisation)
Are cannabis products that are not approved in Denmark but for which the doctor can apply for dispensing approval from the Danish Medicines Agency? Under this scheme, the medicine can be imported from, e.g. the USA and prescribed to specific patients if the Danish Medicines Agency approves the doctor's application.
Marinol and Nabilone: Other countries, such as the USA, have approved the medicines Marinol and Nabilone. They contain synthetically produced cannabinoids. The manufacturers of Marinol and Nabilone have not applied for approval in Denmark. Therefore, Marinol and Nabilone are not sold as approved medicines in Denmark.
Criteria for prescribing medicinal cannabis
The responsibility for medical cannabis treatment always lies with the treating physician. Therefore, it is the doctor who determines whether a patient should be treated with medicinal cannabis.
According to the cannabis guidelines from the Danish Medicines Agency:
Relevant approved marketed medicines should be tested before treatment with medicinal cannabis is attempted.
Cannabis should not be used in children and adolescents under the age of 18 due to lack of knowledge about long-term effects, including cognitive development.
A doctor can only prescribe a maximum of one month's use per prescription.
Doctors generally do not treat with medicinal cannabis outside of their specialty area.
Furthermore, the Danish Medicines Agency has approved a few patient groups and indications, including chronic pain conditions, for the use of medicinal cannabis as a patient in Denmark. You can read more about relevant indications for prescription here.
References
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Ito, A. & Yoshimura, M. Mechanisms of the analgesic effect of calcitonin on chronic pain by alteration of receptor or channel expression. Mol Pain13, (2017).
Tzschentke, T. M. Pharmacology of bisphosphonates in pain. Br J Pharmacol178, 1973–1994 (2021).
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Bilbao, A. & Spanagel, R. Medical cannabinoids: a pharmacology-based systematic review and meta-analysis for all relevant medical indications. BMC Med 20, (2022).
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Ferro, E. S. et al. Cannabinoid Therapeutics in Chronic Neuropathic Pain: From Animal Research to Human Treatment. (2021) doi:10.3389/fphys.2021.785176.
de Vita, M. J., Moskal, D., Maisto, S. A. & Ansell, E. B. Association of Cannabinoid Administration With Experimental Pain in Healthy Adults: A Systematic Review and Meta-analysis. JAMA Psychiatry 75, 1118–1127 (2018).
Boehnke, K. F., Litinas, E. & Clauw, D. J. Medical Cannabis Use Is Associated With Decreased Opiate Medication Use in a Retrospective Cross-Sectional Survey of Patients With Chronic Pain. J Pain 17, 739–744 (2016).
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