Managing Chronic Pain

Pain Medication and management techniques

Introduction

Chronic pain (CP) is recognized as a major public health issue with significant economic and social consequences.

Additionally, this condition not only has an impact on the patient (both as a sensory and emotional problem) but also on his or her family and social network.

Chronic pain is one of the most prevalent complaints seen in an outpatient clinics, affecting over 25% of Americans.

The inability to control chronic pain and the opioid dependency brought on by it can have serious consequences for morbidity and mortality.

A variety of methods for managing chronic pain are discussed in this article, but first, what exactly is chronic pain?

What is Chronic Pain?

Pain is a common sign of many illnesses and typically indicates the presence of tissue damage. Even though pain is unpleasant, it also serves as a helpful mechanism for promoting healing because it forces the sufferer to rest the injured area and seek medical attention.

Chronic pain is a term used to describe pain that lasts for long durations of time as a result of a disease process or after the typical healing time for an injury.

Chronic pain is defined by the International Association for the Study of Pain (IASP) as pain that persists for more than 3 months.

It is likely to develop as a result of small, cumulative changes in lifestyle made to cope with acute musculoskeletal pain and is most likely the result of a combination of behaviors, beliefs, and emotions.

Chronic Pain Management Practices

Chronic pain is treated with a personalized, step-by-step, multimodal approach that includes pharmacotherapy, psychotherapy, integrative treatments, and interventional procedures.

Paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and adjunctive therapies like steroids, anti-inflammatories, and antidepressants are all important pharmacological options in the management of chronic pain.

1.  

Analgesics, NSAIDs and Opioids

a.   

     Paracetamol

The preferred medication for treating mild to moderate persistent pain is paracetamol.

Many patients who have tried and failed to control their pain with paracetamol have been given insufficient doses to provide pain relief.

Increasing the dose or taking doses regularly may be enough to effectively manage the pain.

It is crucial to emphasize that paracetamol should be taken on a regular and timely basis, not based on the presence of pain.

Paracetamol has a better adverse-effect profile than NSAIDs and can be used safely in the long term with medical supervision if the maximum dose is not exceeded.

b.    NSAIDs

NSAIDs are valuable analgesics, with a low risk of significant unfavorable consequences, when used correctly in cautiously selected patients.

The primary indication for both nonselective NSAIDs and the more selective cyclooxygenase 2 (COX-2) inhibitors are mild to moderate pain, especially that of musculoskeletal origin.

NSAIDs may be beneficial for chronic pain caused by underlying inflammatory mechanisms (e.g., arthritis).

There are many risk factors to take into account when choosing an agent, one of which is age.

The risk of thrombotic events is relatively low with naproxen and low-dose ibuprofen compared with other NSAIDs.

Proton-pump inhibitors are recommended for people over 45 who have been taking an NSAID for more than three months.

Mechanism of Action

The primary mechanism of action of NSAIDs is the inhibition of the enzyme cyclo-oxygenase (COX), which results in the blockade of prostaglandin synthesis.

NSAIDs' analgesic effects result from both peripheral actions on the COX enzyme and effects on the central nervous system.

Side Effects

In addition to drug-drug interactions, NSAIDs are linked to cardiovascular risk, gastropathy, renal toxicity, platelet inhibition, and other side effects.

c.   

     Opioids

The addition of an opioid is suggested to manage chronic pain if paracetamol and NSAIDs are ineffective at managing the pain or if NSAIDs are contraindicated.

When paracetamol alone is insufficient or if an NSAID is ineffective for treating a patient's pain, a weak opioid may be considered as an alternative (with or without paracetamol).

A weak opioid should be added as a separate tablet so that the full paracetamol dose can be given and the opioid dose can be titrated to effect and tolerability.

It might be possible to switch to a combination tablet with an equivalent dosage once you've found a stable effective dose.

A dose of around 60 mg of codeine per day is usually required, but the lowest dose that can control the patient's pain should be used.

When other analgesics are ineffective or inappropriate due to side effects, strong opioids can be used to relieve pain.

Morphine is widely regarded as the first-choice strong opioid due to its familiarity, low cost, and wide range of formulations.

For those who cannot tolerate morphine, there are alternatives like oxycodone and hydromorphone.

A multidisciplinary pain clinic or a pain specialist should preferably be consulted before a strong opioid is prescribed for a patient.

Opioids should only be used when the potential benefits outweigh the potential risks, which is typically when other therapies have failed to adequately relieve pain and improve function.

Opioids should always be used in conjunction with nonpharmacologic and nonopioid pharmacologic therapy, and they should be carefully monitored for benefit, risk, and treatment adherence.

d.   

Combinations

There are many different combinations of drugs that can be used to treat pain.

Although compound analgesics have a stronger effect when treating acute pain, numerous additive ingredients, such as caffeine and antihistamines, can frequently have undesirable side effects when treating chronic pain.

However, when using opioids and NSAIDs specifically, paracetamol combined with these medications works better than either one alone and lowers the dosage of opioid or NSAID needed to treat pain.

2.   Adjunctive Medications

Adjuvant medications are those that don't contain paracetamol, NSAIDs, or opioids but are still used to treat chronic pain.

Adjunctive agents include tricyclic antidepressants, antiepileptic drugs, muscle relaxants (baclofen), corticosteroids, bisphosphonates, and calcitonin.

They have frequently been used efficiently in cases where chronic pain has a neuropathic origin.

Although the substances aren't formally categorized as analgesics, research has shown that they can be beneficial in many chronic pain syndromes.

They provide analgesia by improving endogenous pain control and increasing activity of the descending inhibitory pathway; However, this is still not clear.

Pain relief from selective serotonin reuptake inhibitors (SSRIs) is minimal.

a.   

     Antidepressants

Antidepressants are frequently prescribed to people with chronic pain for both pain relief and the comorbid treatment of depression and sleep issues.

Antidepressants may be beneficial for a variety of pain conditions, including low back pain, neuropathic pain, central sensitization, and nociplastic pain, such as fibromyalgia.

It has been proven that amitriptyline, nortriptyline, and desipramine are effective analgesics independent of their antidepressant effects.

I-            Tricyclic antidepressants (TCAs)

TCAs are effective treatments for a variety of chronic pain conditions, with or without coexisting depression, although none of the TCAs have a primary indication for pain management on the US Food and Drug Administration (FDA).

Tricyclic antidepressants are considered the first line of systemic treatment for a wide range of neuropathic pain syndromes, including diabetic neuropathy.

Tricyclic antidepressants are believed to have an inhibitory effect on nociceptive (pain) pathways by preventing the reuptake of serotonin and norepinephrine, though the exact mechanism of the analgesic action is unknown.

Amitriptyline is one of the TCAs with the strongest sedative and anticholinergic effects. As a result, it is rarely used as the first-line TCA for chronic pain, unless sleep initiation and maintenance are a problem.

The most frequent side effects of tricyclic antidepressants are linked to their anticholinergic activity including (constipation, dry mouth, blurred vision, cognitive changes, tachycardia, and urinary hesitation).

Other common side effects include orthostatic hypotension, falls, weight gain, and sedation.

II-           Serotonin-norepinephrine reuptake inhibitors (SNRIs)

Venlafaxine and duloxetine are SNRIs that have been used to treat peripheral neuropathic pain.

Milnacipran and duloxetine have both been used to treat fibromyalgia, but duloxetine has the best evidence of efficacy for reducing chronic musculoskeletal pain.

Duloxetine is an antidepressant that has the most evidence to support its analgesic efficacy of any antidepressant. It is also FDA-approved for the treatment of fibromyalgia, chronic low back pain, osteoarthritis, and painful diabetic neuropathy.

The most frequent side effects are dizziness, fatigue, dry mouth, nausea, insomnia, drowsiness, constipation, and nausea.

b.    Antiepileptic agents

Antiepileptic drugs are among the preferred adjunctive medications for neuropathic pain of various types.

Antiepileptic drugs such as phenytoin, carbamazepine, and divalproex have been used to treat neuropathic pain for many years.

Other medications, like gabapentin and lamotrigine, have a wider application in the treatment of chronic pain.

The analgesic activity of carbamazepine, phenytoin, and valproic acid is believed to be associated with increased membrane stability, a mechanism associated with seizure control.

Clonazepam enhances γ-aminobutyric acid (GABA) _A-receptor-mediated inhibition, and gabapentin is intended to be a GABA analog, but its true mechanism of action is unknown.

Carbamazepine has traditionally been the most commonly used antiepileptic drug for pain.

Other antiepileptic medications, such as gabapentin and lamotrigine, may be more effective for painful neuropathies.

Antiepileptic medications are especially helpful for patients who experience lancinating or burning pain.

For neuropathic pain associated with cancer that is unresponsive to tricyclic antidepressants, antiepileptic medications may be helpful as an adjunct to opioids.

Additionally, they can be used for patients who are unable to tolerate tricyclic antidepressants and those who experience myoclonic jerks as a result of high-dosage opioid therapy.

I-            Gabapentin

Neuropathic pain should be easier to control with gabapentin.

Its use is currently supported by evidence in the treatment of central poststroke pain, reflex sympathetic dystrophy, diabetic neuropathy, trigeminal neuralgia, postherpetic neuralgia, radiation myelopathy, and neuropathic cancer pain.

Gabapentin is recommended as first-line antiepileptic therapy by some pain specialists because it is well tolerated and does not have the drug interactions associated with carbamazepine.

Gabapentin commonly causes somnolence, dizziness, ataxia, and fatigue.

Nystagmus, tremor, and diplopia are less commonly reported side effects.

II-           Carbamazepine

Carbamazepine has a fast onset of analgesic action and has traditionally been used as the first-line antiepileptic drug in the treatment of diabetic neuropathy.

It has been proven to be effective in treating the pain brought on by diabetic neuropathy and is the most frequently used medication to treat trigeminal neuralgia.

Adverse effects differ depending on the dosage and method of administration.

The most prevalent side effects are nystagmus, dizziness, diplopia, lightheadedness, and lethargy, which are either dose-dependent or transient.

Additionally, possible side effects include gastrointestinal issues, syndrome of inappropriate antidiuretic hormone secretion, cognitive impairment, and effects on mood and sleep (such as agitation, restlessness, irritability, and insomnia).

A headache, diplopia, dysarthria, and ataxia may appear at higher serum concentrations.

c.    Muscle relaxants

The use of muscle relaxants (e.g., methocarbamol, metaxalone, carisoprodol) for chronic pain patients is avoided and not recommended.

Muscle pain and occasionally spasm can be present in conjunction with a wide range of pain conditions. There is no proof that these drugs relax muscles.

Although muscle relaxants have a variety of pharmacologic effects, none of them directly affect the muscle itself.

Pain relief and spasm relief without spasticity may be due to CNS effects, such as sedation, rather than analgesic effects.

Anti-spasticity medications, such as baclofen or tizanidine, may reduce the pain caused by persistent tonic muscular contractions when true muscular spasticity is present.

d.    Acupuncture

Acupuncture is a controversial treatment for chronic pain, owing to its origins outside of biomedicine.

Acupuncture is a practice of traditional Chinese medicine in which the body's internal balance is restored using needles.

According to recent studies, acupuncture is effective in treating five types of pain: low back pain (LBP), migraines, fibromyalgia, neck pain, and abdominal pain.

A meta-analysis of nearly 18,000 randomized participants from 25 high-quality trials found that acupuncture is an effective treatment option for patients suffering from back and neck pain, osteoarthritis, chronic headache, and shoulder pain.

3.    Topical Analgesics

Topical analgesics have likely existed for as long as medicine itself.

Topical analgesics have several advantages, including fewer drug-drug interactions, fewer side effects, reduced or absent first-pass metabolism, improved patient compliance, and the ability to apply directly to the painful site.

Topical analgesics come in sprays, creams, gels, solutions, ointments, and patches.

Lidocaine and topical non-steroidal anti-inflammatories (NSAIDs) are frequently used alone.

Topical analgesics that are less commonly used, such as gabapentin, ketamine, and baclofen, are usually used in a compounded topical cream with three or more medications.

a.    Topical nonsteroidal anti-inflammatory drugs (NSAIDs)

Topical NSAIDs, which come in gel, spray, or cream form, can relieve acute musculoskeletal pain and may be helpful for patients with single-joint osteoarthritis.

NSAIDs inhibit cyclooxygenase activity, lowering levels of prostaglandins, prostacyclins, and thromboxanes and thus alleviating inflammatory pain.

NSAIDs may also reduce pain via a secondary mechanism, attenuating spinal nociceptive transmission by inhibiting the COX-2 subtype of cyclooxygenase.

Two topical NSAID formulations for treating OA (osteoarthritis) have received FDA approval: diclofenac sodium topical 1.5% solution in 45.5% dimethyl sulfoxide (D/DMSO), which is only approved for treating osteoarthritis of the knee, and diclofenac sodium 1% gel (DG), which is approved for treating osteoarthritis of the elbows, wrists, hands, knees, ankles, and feet.

The FDA has only approved the use of a diclofenac epolamine 1.3% patch (DP) for treating sprains and strains in the US.

Since topical NSAIDs have lower systemic absorption than their oral formulation, the risk of gastrointestinal, renal, and cardiovascular toxicity is significantly lower.

Topical NSAIDs may be better tolerated than oral preparations, with the most commonly reported side effect being mild skin rashes.

b.    Topical Lidocaine

Lidocaine, an amide-type local anesthetic, reduces voltage-gated sodium-channel activation, preventing action potential generation and thus inducing anesthesia.

Topical lidocaine reduces neuropathic pain by selectively inhibiting Aδ and C fibers in a way that lessens pain while maintaining normal sensation.

Additionally, it activates the irritant receptor TRPV1, which most likely explains why the initial exposure causes a burning sensation.

Some forms of neuropathic pain are treated with topical lidocaine, which is regarded as a secondary therapy.

Topical lidocaine is often used as a patch or plaster to treat chronic pain.

The strongest evidence points to its potential benefits for painful diabetic neuropathy as well as postherpetic neuralgia.

Long-term application results in increased thresholds for touch, pinprick, and mechanical windup as well as a slight loss in epidural nerve fiber density.

Topical lidocaine is typically prescribed as a 5% transdermal lidocaine patch (LP), which is applied for up to 12 continuous hours per day and can be cut to more precisely fit the dimensions of a painful area.

Lidocaine patches should only be used on intact skin to avoid excessive systemic lidocaine absorption.

In the US, they are approved for the treatment of postherpetic neuralgia (PHN).

Up to one-third of people who use lidocaine patches might develop irritant contact dermatitis.

Additionally, lidocaine comes in gel and ointment forms.

In comparison to patches, these may be more practical for use on painful toes or other small areas, but they require more frequent application and have a tendency to rub off on clothing.

Applying topical lidocaine to healthy skin is typically safe.

c.    Topical Capsaicin

Capsaicin has been used to treat postherpetic neuralgia, HIV neuropathy, diabetic neuropathy, and osteoarthritis in one or a few joints.

Capsaicin is an agonist of transient receptor potential vanilloid member 1 (TRPV1), a receptor found in small nerve fibers (a delta and c fibers) involved in pain.

Analgesia is most likely caused by short-term desensitization and long-term de-functionalization of nociceptor terminals, both of which have a dose-dependent impact.

It is available without a prescription as a low-concentration (up to 0.1%) cream, lotion, or gel and by prescription as a high-concentration (8%) patch.

To reduce local pain, the 8% patch is typically used in conjunction with pretreatment with topical or injected lidocaine, as well as other stronger oral or IV analgesics.

Before optimum pain relief can be attained, low-concentration capsaicin preparations must be applied three to four times daily over the entire painful area for up to six to eight weeks.

Capsaicin's primary side effects include burning, stinging, and erythema (relaxation) at the application site, which can cause intolerance in up to one-third of patients.

4.   Using Transcutaneous electrical nerve stimulation (TENS)

Transcutaneous electrical nerve stimulation (TENS) is a low-cost nonpharmacological intervention used to treat acute and chronic pain.

These small battery-powered devices deliver alternating current through cutaneous electrodes placed near the painful area.

The pulse frequency and intensity parameters are adjustable and linked to TENS efficacy.

It activates a complex neuronal network for pain relief by activating the descending inhibitory systems of the central nervous system to reduce hyperalgesia.

Regarding the effectiveness of TENS application for specific types of pain or pain conditions, there is general disagreement in the scientific literature.

While a significant body of work exists that suggests that TENS is effective for neuropathic, nociceptive, and musculoskeletal pain, a notable portion of these studies were noted to have methodological concerns.

5.   Relaxation Techniques

Relaxation is one example of a non-pharmacological treatment that is becoming more widely accepted as a pain-reduction and pain-coping intervention.

It is considered of the most affordable and widely accessible treatments for chronic pain. There are no known negative effects as well.

A relaxed state frequently includes feelings of psychological and bodily well-being and calmness.

The goal of relaxation techniques is to decrease sympathetic nervous system (fight or flight) activity by inducing a relaxation response, which is the opposite of the stress response.

There are many reasons why using relaxation techniques can lessen chronic pain.

One explanation is that relaxation techniques lessen chronic pain by triggering pain-inhibitory brain processes, which further affect the perception of pain.

Relaxation techniques are likely to be most effective in the long run when used regularly over time.

Studies demonstrate that relaxation techniques have a pain-reducing effect on patients with chronic pain and have an impact on secondary outcome measures.

However, relaxation techniques should be added to existing treatment plans rather than used as a standalone treatment.

6.   Deep and Slow Breathing (DSB)

The practice of deep and slow breathing (DSB) is widely used in the treatment of a wide range of diseases, including psychiatric disorders like anxious and depressive syndromes or disorders caused by stress, as well as somatic disorders and hypertension and pulmonary diseases.

When it comes to treating chronic pain syndromes, DSB techniques are incorporated into multimodal treatment plans because they are a part of many physical, mental, and spiritual disciplines like yoga, Qi-Gong, or Tai Chi.

In this context, relaxation may be essential for breathing techniques to become a successful treatment for pain and stress-related disorders.

7.   Massage Therapy

Massage therapy is defined as the patterned and purposeful manipulation of soft tissue for therapeutic purposes for the prevention or reduction of pain, spasm, tension, or stress, as well as the promotion of health and wellness.

It has several attractive aspects, including the fact that no special equipment is required for application and that it is delivered safely.

Massage has many benefits for patients with drug allergies and poses no significant risks or adverse effects. It is also highly secure, inexpensive, and convenient operation.

Research studies have shown that massage therapy is useful for managing pain.

8.   Exercise

Exercise causes our bodies to release endorphins, which are naturally occurring painkillers, sedatives, and antidepressants.

Endorphins prevent pain signals from reaching the brain and produce a natural high feeling, resulting in a sense of relaxation and, as a result, reduced pain.

The body then becomes 'deconditioned' when people rest due to pain or fear of pain. When this occurs, new issues arise that make the pain worse.

The medical and scientific communities generally concur that physical/reconditioning exercise and weight loss are crucial in the treatment of chronic pain because they lessen both pain intensity and functional impairment.

Before starting any physical conditioning or weight loss program, always consult a doctor.

References

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2.     Chronic Pain - Statpearls -NCBI Bookshelf.

3.     An Overview of Treatment Approaches for Chronic Pain Management.

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6.     Adjunctive Agents in the Management of Chronic Pain.

7.     UpToDate pharmacological management of chronic pain in adults

8.     Comprehensive Review of Topical Analgesics for Chronic Pain.

9.     Vickers, Andrew J, et al.“Acupuncture for Chronic Pain: Update of an Individual Patient DataMeta-Analysis.” The Journal of Pain, U.S. National Library of Medicine,May 2018

10. “The Role of Acupuncture in theTreatment of Chronic Pain.” Best Practice & Research ClinicalAnaesthesiology, Baillière Tindall, 8 Aug. 2020

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12. Using Tens for Pain Control:The State of the Evidence.

13. Transcutaneous ElectricalNerve Stimulation - Statpearls - NCBI Bookshelf.

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