All you need to know about pain treatment: approaches, types and advances

Pain, a universal and complex experience, represents a major public health challenge worldwide. In France, the National Institute of Health and Medical Research (Inserm) estimates that it is the cause of two-thirds of medical consultations. Even more alarming, no less than 12 million French people suffer from so-called "chronic" pain, that is, pain that persists beyond three months, that responds poorly to conventional treatments and that considerably affects the quality of life of patients, both personally and professionally. This phenomenon increases with age and has a female predominance.

Far from being a simple symptom, chronic pain becomes a disease in its own right when it becomes long-lasting, thus losing its function as a warning signal. Faced with this reality, research and healthcare professionals are making considerable efforts to better understand its mechanisms and, above all, to improve its management. This article aims to explore in depth the different facets of pain management, from its fundamental understanding to the most innovative therapeutic strategies.

Understanding pain: an essential step to better treat it

To understand pain management, it is imperative to grasp its nature. The International Association for the Study of Pain (IASP) defines it as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage." This definition underscores its subjective and multidimensional nature, involving both physical sensations and emotions.

There is not just one form of pain, but several types, each with distinct characteristics, even if there may be complex overlaps in some patients. Sources primarily identify three categories of pain, classified according to their nature and duration.

• Nociceptive pain: These are directly related to the stimulation of nociceptors, specialized receptors activated by potentially damaging stimuli. These stimuli can be a blow, joint inflammation, or excessive heat. The information captured by the nociceptors is conveyed through specific nerve pathways to the brain, where it is interpreted, particularly at the level of the cerebral cortex. This type of pain is often described as a warning signal useful for etiological diagnosis.
• Neuropathic pain: Unlike nociceptive pain, these are caused by damage to nerve fibers or the central nervous system itself. They can occur, for example, during shingles (reactivation of the chickenpox virus), diabetes, or following an amputation. They are often described as sensations of burning, tingling, electric shocks, numbness, or stabbing. Minimal touching can cause unbearable pain, a phenomenon called allodynia or hyperalgesia, characteristic of these pains. They are sometimes misunderstood by patients and caregivers, and may even be located away from the nerve lesion itself.
• Nociplastic pain: These pains are sensations sometimes similar to neuropathic pain, but they are often generalized throughout the body and are not associated with visible damage to nerve fibers. They are more likely due to a dysfunction of the pain detection and control system itself, leading to an exaggeration of the nerve message and/or an over-interpretation of this message by the brain. Fibromyalgia, characterized by widespread and persistent pain, sensitivity to pressure, intense fatigue, and sleep disturbances, is an example. There is also genuine pain without visible injury, often called dysfunctional pain.

Pain is a multidimensional syndrome and its functioning is complex. The brain plays a central role, as it is the one that "commands" the pain. It has three well-mapped components within the brain:

• The sensory-discriminative component: It allows to locate the pain and assess its intensity. A dysfunction can lead to a generalization or extension of the localized pain.
• The affective-emotional component: It determines the emotion associated with pain. Excessive emotional intensity may require the investigation of anxious or depressive repercussions.
• The cognitive-behavioral component: Painful information is linked to anxiety and memorized, influencing future behaviors. An overly powerful component can lead to kinesiophobia (fear of movement).

The intensity of pain can be modulated by the context (family, professional, social), emotions, level of anxiety, and depression. The memory of past painful experiences can also reinforce its perception. It is important to note that there is not always a direct link between the extent of an injury and the intensity of the pain felt. Examinations may be normal despite intense pain, either because the lesion is invisible (too small, early stage) or because the pain is multifactorial.

Pain assessment: the key to personalized management

Accurate pain assessment is a fundamental prerequisite for any effective management. The patient is the central player in this assessment, because no one is better placed than them to describe their pain, quantify its intensity, and determine where and when it manifests. They are also the only ones who can judge the effectiveness of treatments and their relief.

Unlike many medical conditions, there is no radiological or biological test to objectify pain; there is no "pain marker." Evaluation therefore relies on the patient's ability to communicate and describe their feelings. For people who are able to express themselves, several self-assessment scales are used by healthcare professionals:

• The Visual Analog Scale (VAS): It is in the form of a ruler. The patient positions a cursor on a line ranging from "No pain" to "Maximum imaginable pain." The caregiver reads the corresponding value on a scale from 0 to 10.
• The Numerical Rating Scale (NRS): Simpler, it asks the patient to rate their pain from 0 (no pain) to 10 (maximum imaginable pain). It is widely used because it does not require support.
• The Simple Verbal Scale (SVS): It allows to describe the intensity of pain with simple words: "no pain", "mild", "moderate", "intense (strong)", "very intense (very strong)". Although less precise, it is often preferred for the elderly because it is easy to understand.

These scales (VAS, NRS, VRS) provide information on the overall intensity, but do not provide information on the causes or mechanisms of the pain. In the event of a discrepancy between what the patient expresses and what the caregiver observes, the professional must believe the patient and adapt the scale used, seeking to understand the discrepancy.

The challenge of assessment becomes more complex when the patient is unable to express themselves verbally, such as young children, elderly people with loss of autonomy, or people with multiple disabilities. In these situations, any change in behavior may be a sign of pain. Caregivers and relatives should be particularly vigilant to bodily and behavioral signals, such as moans, grimaces, stiffness, agitation, protective gestures, withdrawal, refusal to eat, sleep disturbances, or irritability. Specific observation grids have been developed for these populations, allowing to identify the signals and assess the intensity of the pain. Among them are:

• For children: the EDIN, HEDEN, EVENDOL scales, the faces scale, the vertical VAS, the San Salvadour grid (or DESS), the modified FLACC scale (from birth to 18 years). There is also a pediatric DN4 scale for neuropathic pain.
• For elderly and/or non-communicative people: the Doloplus2® scale, the Algoplus® scale, the Behavioral Scale for Elderly People (ECPA).
• For adolescents and adults with multiple disabilities: the EDAAP (Assessment of Pain Expression in Adolescents or Adults with Multiple Disabilities), the EDD (Assessment of Pain Expression in Dyscommunicating People), the GED-DI (Pain Assessment Grid - Intellectual Disability), the ESDDA (Simplified Scale for Pain Assessment in Dyscommunicating People with Autism Spectrum Disorder).

Communication is essential. Healthcare professionals must systematically inform the patient about the treatment to be carried out and the analgesia methods to be used. Pain caused by care is predictable and must be systematically prevented and treated, as it can lead to anxiety, exhaustion and even refusal of care.

Pharmacological pain treatments

The drug management of pain (see our article on Nefopam) is adapted to its origin, intensity, duration and location. The practitioner chooses the treatment methods according to the type of pain (chronic, post-operative, related to care, migraine, etc.), following best practice recommendations. The objective is to counteract the mechanism of pain and act according to its characteristics, favoring well-tolerated drugs and taking into account the patient's history.

Conventional analgesics are the first-line treatment for nociceptive pain, whether acute or chronic. They come in different pharmacological classes, from the mildest to the most potent:

• Paracetamol.
• Some non-steroidal anti-inflammatory drugs (NSAIDs).
• Opioids, which can be weak or potent.

Opioids are a major class of analgesics. They act by mimicking the action of endogenous opioids (endomorphin or endorphin) produced naturally by the body, mainly in the central nervous system (brain and spinal cord) and peripheral nervous system. We distinguish:

• Weak Opioids (Level 2): codeine, dihydrocodeine, tramadol, opium. They are prescribed for moderate nociceptive pain, immediately or in case of failure of Level 1 analgesics.
• Strong Opioids (Level 3): alfentanil, fentanyl, hydromorphone, morphine, oxycodone, pethidine, sufentanil, tapentadol. Morphine is the first-line strong opioid for cancer pain. They are recommended for intense, acute, subacute (surgery, emergencies), persistent or recurrent nociceptive pain (cancer), and in certain specific situations in case of failure of first-line treatments.

Titration is an essential method for rapidly adjusting the dosage of an opioid, often performed in the recovery room for postoperative pain. Opioids can be administered via various routes: intravenously, subcutaneously, or orally. For continuous pain, a background treatment (daily) is necessary, supplemented by breakthrough doses (additional immediate-release doses) for transient pain flares.

Opioids, like all drugs, can cause undesirable effects, the most frequent being constipation (almost inevitable with chronic administration, and requiring preventive measures from the very first dose) and somnolence (which generally diminishes after a few days of titration). Other effects such as nausea, vomiting, sweating, nightmares, disturbances of attention, concentration and memory, hallucinations and myoclonus (involuntary muscle twitching) may occur. In the event of intractable side effects or ineffectiveness, opioids may be rotated.

It is important to emphasize that opioids are not always indicated for all types of pain. They have little to no effect on neuropathic pain and should not be used for primary headaches (including migraines) or nociplastic pain (fibromyalgia). The fear of morphine addiction is a misconception; its use in the post-operative period or for its analgesic action does not create drug addiction or dependence. Discontinuation of strong opioid treatment should always be done under medical advice, with a gradual reduction in doses.

In addition to conventional analgesics, physicians may use other molecules that have an analgesic effect without it being their primary purpose, particularly for chronic neuropathic pain. This is the case with certain antidepressants or antiepileptics, which act specifically on the mechanisms of this pain. It is important to note that their prescription in this context does not mean that the patient is considered depressive or epileptic. Unfortunately, they are only effective in one out of two patients.

Local pharmacological treatments are also available for chronic pain. These include lidocaine patches (a local anesthetic) or capsaicin patches. Botulinum toxin injections can also be performed for certain localized neuropathic pain, with an effect lasting several months.

Combining medications with complementary actions can maximize effectiveness while limiting side effects (e.g., paracetamol or NSAIDs with an opioid). It is generally not recommended to combine medications from the same family to avoid overdoses. Regarding the route of administration, the common misconception that injection is more effective than the oral route is often false; the oral route is often comparable in effectiveness and avoids the painful act of injection.

In cases of persistent pain despite treatment, several situations can be considered: the pain mechanism no longer corresponds to the drug's mode of action, the dose, route, or frequency of administration are inadequate, or there is variability in individual response. Medical monitoring is essential to adjust the treatment. It is recommended to take analgesics before the pain becomes too severe, as persistent acute pain can perpetuate itself and become chronic. Analgesics do not interfere with examinations, and it is even recommended to treat the pain as a priority to allow the examinations to be carried out under good conditions.

Non-pharmacological approaches: an essential dimension

Beyond medication, numerous non-drug techniques play a key role in pain management, particularly chronic pain. They are complementary to drug approaches and can be very useful. In some cases, for chronic pain, the proportion of medication may even be very limited (less than 30%) in the overall management.

These approaches fall into several categories:

1. Physical approaches :
   • Physiotherapy.
   • Physiotherapy, including the application of heat, cold, or electrical current.
   • Balneotherapy.
   • Restraints (brace, foam collar, strapping).
   • Postural and gestural education.
   • Exercise reconditioning and functional restoration of the spine, particularly for chronic lower back pain. Strict rest is no longer considered a useful strategy for chronic lower back pain.
2. Electrical or magnetic stimulation :
   • Transcutaneous electrical nerve stimulation (TENS): Electrodes temporarily attached to the skin deliver a low-intensity current to relieve pain. It acts by "closing" the gate to the transmission of pain at the level of the nervous system and/or by stimulating the production of endogenous analgesics (naturally produced by the body). A test session is necessary to adjust the parameters, and the device is used regularly by the patient.
   • Spinal cord electrical stimulation: More invasive, it involves implanting electrodes in the spinal column to inhibit the transmission of painful nerve signals.
   • Repetitive transcranial magnetic stimulation (rTMS): Very promising, it involves applying a powerful magnetic current to the scalp to modify the electrical activity of brain areas involved in pain control. Recent studies have explored its use to identify patients who may benefit from it, particularly for neuropathic pain.
3. Psychophysical methods :These methods address the person in their physical and psychological dimensions, helping to mobilize their own resources. They counter situations of muscular and emotional tension related to pain and stress and can interrupt the vicious pain-tension-stress cycle. They complement drug-based approaches and include:
   • Relaxation.
   • The hypnosis (or hypnoanalgesia) for analgesic purposes.
   • Sophrology.
   • Meditation. These techniques often require learning to allow for autonomous use (self-relaxation, self-hypnosis). When practiced by specifically trained professionals, they are ethical and safe. They can be effective for a large number of situations and types of pain, with varying degrees of effect.
4. Adapted Physical Activity (APA): Often underestimated, physical activity is an important element of balance to maintain or restore in the face of pain. APA is an activity that mobilizes the body in conditions compatible with the patient's health and physical capacities, without causing significant pain during or after exertion, or excessive fatigue. It can ultimately help limit pain. Kinesiophobia (fear of movement) is a behavioral component that leads people with chronic pain to avoid all activity, which is often counterproductive. Healthcare professionals can guide the patient in this project, sometimes as part of rehabilitation programs.
5. Other Therapeutic Options: Some methods like acupuncture, osteopathy, or homeopathy can be effective for some individuals, although their effectiveness is not always scientifically confirmed.

Non-drug management is particularly relevant for specific populations:

• For children, methods such as sucrose or breastfeeding in newborns, distraction, and hypnoanalgesia are fundamental for the prevention of pain related to care. Learning psychocorporeal methods (relaxation, biofeedback, hypnosis) is an effective long-term treatment for migraine in children.
• For elderly and non-communicating multiply disabled people, special precautions are necessary before any painful procedure. In addition to local anesthetics and MEOPA (Equimolar Mixture of Oxygen and Nitrous Oxide), non-drug methods such as the choice of location, the presence of a relative, the use of toys or familiar objects, music, and simple speech are essential.

The Placebo Effect and the therapeutic relationship

The placebo effect is a fascinating and increasingly studied dimension of pain management. A placebo is a substance (or any other means, such as surgery or the action of the therapist himself) that appears to treat a health problem, although it has no demonstrated pharmacological or specific effect for that problem. The placebo effect, for its part, is the non-specific efficacy that is added to the scientifically proven efficacy of any drug or therapeutic act, thus increasing the "total" efficacy of the treatment.

How does this effect work? Several mechanisms are associated with its effectiveness:

• The relationship of trust: Establishing a bond of trust between the caregiver (the one who prescribes or gives) and the patient (the one who receives) is fundamental.
• Patient expectation and belief: The greater the patient's expectation and their belief in the treatment, the greater the effectiveness of the treatment (and therefore the placebo effect) will be.
• The caregiver's conviction: The physician's enthusiasm and conviction for a treatment can also enhance this effect.
• Cognitive and emotional mechanisms: Clear explanations, reassurance, and a supportive attitude from the caregiver not only contribute to trust but also reduce anxiety, a major factor in the placebo effect.
• Neurobiological mechanisms: Pain relief via placebo is underpinned by neurobiological mechanisms of the same nature as the specific effect of an analgesic, notably involving the activation of the body's endogenous opioid systems.

The placebo effect is not limited to analgesic medications; it contributes to the effectiveness of all medications. From an ethical standpoint, in the context of therapeutic trials, the use of a placebo should be accompanied by the possibility of prescribing rescue analgesics if the pain level reaches a predefined threshold.

To maximize the effectiveness of a treatment, it is advisable to enhance the placebo effect. This involves developing a good relationship of trust between patients and healthcare providers, which is called the therapeutic alliance. This alliance is one of the essential components of a successful treatment, along with the accuracy of the information transmitted and the resulting confidence. When the patient understands and accepts the action of the medication, they expect a perceptible relief, which reinforces the overall effectiveness.

Psychology and pain: a complex interaction

The question of whether pain manifests "in the head" is frequent. According to the IASP definition, pain is an unpleasant experience, both sensory and emotional. This means that it is experienced simultaneously on the physical and psychological level, regardless of its origin. There is therefore no physical pain without a psychological counterpart, and reciprocally, no psychological disorder without physical correlation.

Sometimes, the pain felt in the body may be the unconscious expression of an underlying psychological difficulty (trauma, bereavement, separation). However, it is essential to emphasize that treating chronic pain exclusively with psychotherapy is pointless. On the contrary, a multidisciplinary approach is essential, and the psychologist makes a valuable contribution to the diagnosis.

The psychological state strongly influences the perception of pain. Pain is more difficult to bear in the presence of anxiety or depression, which are aggravating factors that need to be identified and managed. Chronic pain can cause depressive disorders through exhaustion, and conversely, a depressive illness can be expressed mainly in painful form. The symptoms of depression and chronic pain are often similar: fatigue, nervousness, loss of appetite, sleep disorders, loss of pleasure. Chronic anxiety, especially in the form of a crisis, is also manifested by various painful bodily signs. Post-traumatic stress situations can evolve into intractable pain requiring specific and comprehensive management.

The patient's lifestyle can also influence pain. This is often a circular system: lack of sleep worsens pain, and pain disrupts sleep; poor diet can influence the painful experience; overactivity may seem to distract from the pain but exhausts the body and reinforces it. A comprehensive approach must therefore focus on lifestyle and consider adjustments.

It is unfortunately common for pain whose cause is not immediately found to be described as "psychosomatic". Sources emphasize that this term is a "catch-all word", often used as a default diagnosis, useless and even stigmatizing. An absence of organic explanation does not in any way mean that the patient is "crazy"; health sciences are not absolute knowledge and a complex situation can be difficult to grasp in all its aspects. The goal is rather to adopt a therapeutic approach that integrates the dialogue between body and mind, which is essential in pain clinics.

When pain becomes unbearable and prevents one from living, it is essential to seek help. A multidisciplinary team can help to rethink daily activities, to sort out what can be adjusted, maintained, or given up. The painful experience permanently alters the perception of oneself, one's abilities, and the relationship with those around one; life will never be "as before", but this experience can be a life lesson that changes one's relationship to existence. In extreme cases where the pain is unbearable and leads to suicidal thoughts, it is vital to reach out to a trusted person or a healthcare professional to seek solutions.

Specialized and multidisciplinary care: chronic pain management structures (CPMS)

Faced with pain that persists for a long time, is complex, and for which the patient feels misunderstood, the attending physician remains the primary contact. After several consultations and attempts to find effective solutions, they may refer the patient to a specialist. However, in certain complex situations, referral to a Specialized Chronic Pain Structure (SDC) will be proposed.

SDCs are healthcare facilities identified and specialized in the management of chronic pain. They meet specific specifications and are certified by the Regional Health Agencies (ARS), with a five-year renewal of this certification. They bring together healthcare professionals from different disciplines (doctors, nurses, psychologists, etc.) who are experts in pain assessment and treatment.

To obtain an appointment in SDC, it is generally necessary to discuss it beforehand with your general practitioner or a specialist, who will assess the relevance of this referral. The patient will often have to fill out a referral questionnaire and return it with an introductory letter from their doctor. The addresses of the SDCs are available via a directory of the Ministry of Health or from the ARS.

The operation of a Pain Center (SDC) is based on individualized care. An initial assessment, which may extend over several long consultations, is carried out. This assessment is fundamental to carrying out an exhaustive bio-psycho-social assessment, which takes into account the biological, psychological and social dimensions of pain. This assessment then makes it possible to develop a personalized therapeutic project, discussed with the patient.

This project may include various treatment modalities:

• Drug therapies.
• Non-pharmacological approaches (hypnosis, relaxation, transcutaneous neurostimulation, etc.).
• Psychological support.
• Specific examinations and technical procedures.
• Sometimes, a short hospital stay or referral to another, more specialized facility is required.

The meeting with professionals such as a psychologist, psychiatrist, or social worker, which may be surprising at first, is justified by the fact that chronic pain has repercussions on all aspects of daily life. It can lead to emotional distress, socio-professional and financial difficulties, and an impact on quality of life and relationships, which in turn amplify the pain. The objective is to take into account all these consequences and implement solutions to mitigate them. The attending physician remains a key player, regularly informed of the patient's progress.

In this pathway, the patient is actively informed of the modalities of the therapeutic project so that they can remain an active participant in their care. They are encouraged to develop behaviors adapted to daily life, to understand their illness and its treatments, to observe their own reactions to better manage crises, and to respect the prescriptions and advice of professionals. Acceptance of help and adaptation of physical, professional, family, and social activities are essential to improve quality of life.

For information, patients are encouraged to turn to reliable resources: healthcare professionals, approved associations (such as France Assos Santé), and reference websites such as the Société Française d'Étude et de Traitement de la Douleur (SFETD), the Centre National Ressources Douleur (CNRD), or the Haute Autorité de Santé (HAS). Patient therapeutic education (PTE) is also a major lever, with validated and free programs that help patients become more autonomous in managing their pain.

Patient rights and advances in research

Pain management is not only a medical issue but also a fundamental patient right, enshrined in French law. Article L.1110-5 of the Public Health Code stipulates that "Every person has the right, given their state of health and the urgency of the interventions it requires, to receive, throughout the territory, the most appropriate treatments and care and to benefit from therapies whose effectiveness is recognized and which guarantee the best health safety and the best possible relief of suffering in light of established medical knowledge." More specific laws, such as the 1999 law on access to palliative care and those of 2005 and 2016 on patient rights and end-of-life care, reinforce this right.

Healthcare professionals also have legal obligations regarding pain:

• The nurse's objective is to "participate in the prevention, evaluation, and relief of pain and physical and mental distress of individuals."
• The physician "must strive to alleviate the patient's suffering by means appropriate to their condition and assist them morally."

Patient rights also include therapeutic education. The 2009 Hôpital Santé Territoires law and the 2015 decree frame the TPE programs, aimed at making the patient more autonomous by facilitating their adherence to treatments and improving their quality of life. Access to these programs is voluntary, free and without charge.

In parallel with this legal framework, pain research is particularly active and has progressed considerably in recent years. These advances are essential to refine treatments and offer new perspectives to patients.

• Genetic variations: It is now known that genetic variations explain the difference in response from one patient to another for the same analgesic, as well as the occurrence of adverse effects. For example, variations in the COMT gene, involved in dopamine secretion, may be linked to an increased risk of pain becoming chronic.
• New players in pain: Scientists have identified new molecules and cells involved in the mechanisms of pain. The immune system, metabolic disorders, and the intestinal microbiota may also play a role in the chronification of pain.
• Cerebral Imaging: Advances in medical imaging have enabled the visualization, and even quantification, of pain, leading to a better understanding of the structural and functional changes in the brain areas that process pain information in cases of chronic pain.
• Understanding the types of pain: Knowledge of the different types of pain has become more refined, with each type being transmitted by distinct nerve pathways.
• Fundamental discoveries: In 2021, the Nobel Prize in Medicine rewarded the discovery of TRP and PIEZO channels, involved respectively in thermal and mechanical nociceptors, opening new avenues for analgesic research.
• Promising proteins: Aziz Moqrich's team has discovered the TAFA4 protein, showing in rodents a powerful action against inflammatory, neuropathic and post-operative pain, with a longer duration of action than conventional painkillers such as opioids. The protein is also thought to have a reparative effect on damaged tissue, which could prevent chronic pain. A Phase I clinical trial in humans is expected shortly.
• Therapeutic targets: New therapeutic targets for chronic inflammatory pain are being identified.

Although significant progress has been made, intense research is still needed to improve the management of chronic and inflammatory pain, the mechanisms of which are complex and vary from patient to patient.

In conclusion, pain management is a constantly evolving field, requiring a holistic and multidisciplinary approach. Understanding pain in all its dimensions – sensory, emotional, cognitive, and behavioral – is the first step towards effective relief. The therapeutic arsenal today combines increasingly targeted drugs and various non-pharmacological approaches, all framed by a rigorous evaluation and a relationship of trust between the patient and their care team. Specialized chronic pain structures play an important role for complex cases, while basic research continues to pave the way for even more innovative treatments. The ultimate goal is to alleviate suffering and ensure that no one is left alone in the face of their pain.

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