Analgesic adjuvant

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An analgesic adjuvant is a medication that is typically used for indications other than pain control but provides control of pain (analgesia) in some painful diseases. This is often part of multimodal analgesia, where one of the intentions is to minimize the need for opioids. [1] [2] [3]

Contents

Rationale

Multimodal analgesia refers to the use of multiple classes of medications in order to treat pain from different molecular mechanisms at once. Prolonged use of higher doses of opioids is associated with increased risk of tolerance and opioid use disorder, so there is a growing trend in the use of multimodal analgesia to treat pain. [4] [5] [6]

Types

Anticonvulsants

Anticonvulsants work through blockade of sodium and calcium ion channels to reduce glutamate (excitatory neurotransmitter) release. [7] Nociceptor hyper-excitability, due to damage to pain-transmitting neurons, results in chronic neuropathic pain. Common anticonvulsants used to treat neuropathy are gabapentinoids (calcium channel blockers) and carbamazapine (sodium channel blocker). [8] There is some evidence that anticonvulsants may also help with inflammatory pain through reduction of nociceptor hyper-excitability originally due to damage to surrounding tissue. [9]

Antidepressants

Antidepressants act (as treatment for both depression and pain) by modulating serotonin and norepinephrine neurotransmitter metabolism. Descending serotonin pathways in the spinal cord are implicated in modulation of pain perception, especially in chronic pain. [11] Common agents used are serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs). Duloxetine, venlafaxine, and amitriptyline are all FDA-approved for chronic musculoskeletal pain, peripheral neuropathy, and fibromyalgia). [12] [13] [14]

Muscle relaxants

Over-excitation of skeletal muscle can result in spasticity (increased muscle tone) and/or muscle spasms (involuntary muscle contractions) which may contribute to pain. [15] There are several different types of muscle relaxants used for pain with different mechanisms of action. Muscle relaxants often have sedating effect that contributes to analgesia and improved relaxation. Experts disagree over whether muscle relaxants are useful for acute musculoskeletal pain. [16]

Alpha-2 adrenergic agonists

Alpha-2 adrenergic agonists such as clonidine are traditionally used to treat hypertension via inhibition of norepinephrine release. [17] Central alpha-2 adrenergic activation in the locus ceruleus and spinal cord induce sedation and pain modulation respectively. [17] Clonidine has been shown to have some efficacy when treating both acute and chronic pain. [18]

Related Research Articles

<span class="mw-page-title-main">Analgesic</span> Drugs used to achieve relief from pain

An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in some instances eliminate, sensation, although analgesia and anesthesia are neurophysiologically overlapping and thus various drugs have both analgesic and anesthetic effects.

<span class="mw-page-title-main">Carbamazepine</span> Anticonvulsant medication

Carbamazepine, sold under the brand name Tegretol among others, is an anticonvulsant medication used in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medications and as a second-line agent in bipolar disorder. Carbamazepine appears to work as well as phenytoin and valproate for focal and generalized seizures. It is not effective for absence or myoclonic seizures.

Anticonvulsants are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the excessive rapid firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain.

<span class="mw-page-title-main">Tramadol</span> Opioid pain medication

Tramadol, sold under the brand name Ultram among others, is an opioid pain medication and a serotonin–norepinephrine reuptake inhibitor (SNRI) used to treat moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an hour. It is also available by injection. It is available in combination with paracetamol (acetaminophen).

<span class="mw-page-title-main">Tension headache</span> Medical condition

Tension headache, stress headache, or tension-type headache (TTH), is the most common type of primary headache. The pain usually radiates from the lower back of the head, the neck, the eyes, or other muscle groups in the body typically affecting both sides of the head. Tension-type headaches account for nearly 90% of all headaches.

<span class="mw-page-title-main">General anaesthesia</span> Medically induced loss of consciousness

General anaesthesia (UK) or general anesthesia (US) is a method of medically inducing loss of consciousness that renders a patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general anaesthetic medications, which often act in combination with an analgesic and neuromuscular blocking agent. Spontaneous ventilation is often inadequate during the procedure and intervention is often necessary to protect the airway. General anaesthesia is generally performed in an operating theater to allow surgical procedures that would otherwise be intolerably painful for a patient, or in an intensive care unit or emergency department to facilitate endotracheal intubation and mechanical ventilation in critically ill patients. Depending on the procedure, general anaesthesia may be optional or required. Regardless of whether a patient may prefer to be unconscious or not, certain pain stimuli could result in involuntary responses from the patient that may make an operation extremely difficult. Thus, for many procedures, general anaesthesia is required from a practical perspective.

<span class="mw-page-title-main">Pain management</span> Interdisciplinary approach for easing pain

Pain management is an aspect of medicine and health care involving relief of pain in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals provide some pain control in the normal course of their practice, and for the more complex instances of pain, they also call on additional help from a specific medical specialty devoted to pain, which is called pain medicine.

Diabetic neuropathy includes various types of nerve damage associated with diabetes mellitus. The most common form, diabetic peripheral neuropathy, affects 30% of all diabetic patients. Symptoms depend on the site of nerve damage and can include motor changes such as weakness; sensory symptoms such as numbness, tingling, or pain; or autonomic changes such as urinary symptoms. These changes are thought to result from a microvascular injury involving small blood vessels that supply nerves. Relatively common conditions which may be associated with diabetic neuropathy include distal symmetric polyneuropathy; third, fourth, or sixth cranial nerve palsy; mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; and autonomic neuropathy.

<span class="mw-page-title-main">Venlafaxine</span> Antidepressant medication

Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin–norepinephrine reuptake inhibitor (SNRI) class. It is used to treat major depressive disorder, generalized anxiety disorder, panic disorder, and social anxiety disorder. Studies have shown that venlafaxine improves post-traumatic stress disorder (PTSD). It may also be used for chronic neuropathic pain. It is taken orally. It is also available as the salt venlafaxine besylate in an extended-release formulation.

<span class="mw-page-title-main">Duloxetine</span> Antidepressant medication used also for treatment of anxiety and chronic pain

Duloxetine, sold under the brand name Cymbalta among others, is a medication used to treat major depressive disorder, generalized anxiety disorder, obsessive-compulsive disorder, fibromyalgia, neuropathic pain and central sensitization. It is taken by mouth.

<span class="mw-page-title-main">Amitriptyline</span> Tricyclic antidepressant

Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat major depressive disorder, and a variety of pain syndromes such as neuropathic pain, fibromyalgia, migraine and tension headaches. Due to the frequency and prominence of side effects, amitriptyline is generally considered a second-line therapy for these indications.

<span class="mw-page-title-main">Serotonin–norepinephrine reuptake inhibitor</span> Class of antidepressant medication

Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder (MDD), anxiety disorders, social phobia, chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms. Off-label uses include treatments for attention-deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD), and migraine prevention. SNRIs are monoamine reuptake inhibitors; specifically, they inhibit the reuptake of serotonin and norepinephrine. These neurotransmitters are thought to play an important role in mood regulation. SNRIs can be contrasted with the selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs), which act upon single neurotransmitters.

Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous and/or episodic (paroxysmal) components. The latter resemble stabbings or electric shocks. Common qualities include burning or coldness, "pins and needles" sensations, numbness and itching.

Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certain medications such as benzodiazepines, opioids, stimulants, antiepileptics and antidepressants, as well as the recreational misuse of drugs such as alcohol, opioids and benzodiazepines. The higher the dose used, the greater the duration of use, and the earlier age use began are predictive of worsened physical dependence and thus more severe withdrawal syndromes. Acute withdrawal syndromes can last days, weeks or months. Protracted withdrawal syndrome, also known as post-acute-withdrawal syndrome or "PAWS", is a low-grade continuation of some of the symptoms of acute withdrawal, typically in a remitting-relapsing pattern, often resulting in relapse and prolonged disability of a degree to preclude the possibility of lawful employment. Protracted withdrawal syndrome can last for months, years, or depending on individual factors, indefinitely. Protracted withdrawal syndrome is noted to be most often caused by benzodiazepines. To dispel the popular misassociation with addiction, physical dependence to medications is sometimes compared to dependence on insulin by persons with diabetes.

<span class="mw-page-title-main">Xylazine</span> Veterinary anesthetic, sedative and analgesic

Xylazine is a structural analog of clonidine and an α2-adrenergic receptor agonist, sold under many trade names worldwide, most notably the Bayer brand name Rompun, as well as Anased, Sedazine and Chanazine.

<span class="mw-page-title-main">Dexmedetomidine</span> Anxiolytic, sedative, and pain medication

Dexmedetomidine, sold under the trade name Precedex among others, is a drug used in humans for sedation. Veterinarians use dexmedetomidine for similar purposes in treating cats, dogs, and horses. It is also used in humans to treat acute agitation associated with schizophrenia or bipolar disorder. It is administered as an injection or intravenous solution or as a buccal or sublingual film.

<span class="mw-page-title-main">Lofexidine</span> Medication used for opioid withdrawal

Lofexidine, sold under the brand name Lucemyra among others, is a medication historically used to treat high blood pressure; today, it is more commonly used to help with the physical symptoms of opioid withdrawal. It is taken by mouth. It is an α2A adrenergic receptor agonist. It was approved for use by the Food and Drug Administration in the United States in 2018.

<span class="mw-page-title-main">Alpha-adrenergic agonist</span> Class of drugs

Alpha-adrenergic agonists are a class of sympathomimetic agents that selectively stimulates alpha adrenergic receptors. The alpha-adrenergic receptor has two subclasses α1 and α2. Alpha 2 receptors are associated with sympatholytic properties. Alpha-adrenergic agonists have the opposite function of alpha blockers. Alpha adrenoreceptor ligands mimic the action of epinephrine and norepinephrine signaling in the heart, smooth muscle and central nervous system, with norepinephrine being the highest affinity. The activation of α1 stimulates the membrane bound enzyme phospholipase C, and activation of α2 inhibits the enzyme adenylate cyclase. Inactivation of adenylate cyclase in turn leads to the inactivation of the secondary messenger cyclic adenosine monophosphate and induces smooth muscle and blood vessel constriction.

<span class="mw-page-title-main">Dezocine</span> Opioid analgesic

Dezocine, sold under the brand name Dalgan, is an atypical opioid analgesic which is used in the treatment of pain. It is used by intravenous infusion and intramuscular injection.

References

  1. ↑ Portenoy, Russell K. (April 2020). "A Practical Approach to Using Adjuvant Analgesics in Older Adults". Journal of the American Geriatrics Society. 68 (4): 691–698. doi:10.1111/jgs.16340. ISSN   1532-5415. PMID   32216151. S2CID   214683328.
  2. ↑ Wheeler, Kathleen E.; Grilli, Ryan; Centofanti, John E.; Martin, Janet; Gelinas, Celine; Szumita, Paul M.; Devlin, John W.; Chanques, Gerald; Alhazzani, Waleed; Skrobik, Yoanna; Kho, Michelle E.; Nunnally, Mark E.; Gagarine, Andre; Ergan, Begum A.; Fernando, Shannon (July 2020). "Adjuvant Analgesic Use in the Critically Ill: A Systematic Review and Meta-Analysis". Critical Care Explorations. 2 (7): e0157. doi:10.1097/CCE.0000000000000157. PMC   7340332 . PMID   32696016.
  3. ↑ Hamburger, J.; Beilin, Y. (2019-11-01). "Systemic adjunct analgesics for cesarean delivery: a narrative review". International Journal of Obstetric Anesthesia. 40: 101–118. doi:10.1016/j.ijoa.2019.06.009. ISSN   0959-289X. PMID   31350096. S2CID   198378073.
  4. ↑ Morgan, Michael M; Christie, MacDonald J (October 2011). "Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human". British Journal of Pharmacology. 164 (4): 1322–1334. doi:10.1111/j.1476-5381.2011.01335.x. ISSN   0007-1188. PMC   3229764 . PMID   21434879.
  5. ↑ Kaye, AlanDavid; Urman, RichardD; Rappaport, Yury; Siddaiah, Harish; Cornett, ElyseM; Belani, Kumar; Salinas, OrlandoJ; Fox, CharlesJ (2019). "Multimodal analgesia as an essential part of enhanced recovery protocols in the ambulatory settings". Journal of Anaesthesiology Clinical Pharmacology. 35 (5): S40–S45. doi: 10.4103/joacp.JOACP_51_18 . ISSN   0970-9185. PMC   6515722 . PMID   31142958.
  6. ↑ Olmos, Andrea V.; Steen, Sasha; Boscardin, Christy K.; Chang, Joyce M.; Manahan, Genevieve; Little, Anthony R.; Lee, Man-Cheung; Liu, Linda L. (2021-07-01). "Increasing the use of multimodal analgesia during adult surgery in a tertiary academic anaesthesia department". BMJ Open Quality. 10 (3): e001320. doi:10.1136/bmjoq-2020-001320. ISSN   2399-6641. PMC   8291327 . PMID   34281910.
  7. ↑ Kammerer, M.; Rassner, M. P.; Freiman, T. M.; Feuerstein, T. J. (July 2011). "Effects of antiepileptic drugs on GABA release from rat and human neocortical synaptosomes". Naunyn-Schmiedeberg's Archives of Pharmacology. 384 (1): 47–57. doi:10.1007/s00210-011-0636-8. ISSN   0028-1298. PMID   21533993. S2CID   1388805.
  8. ↑ Sidhu, Harpreet S.; Sadhotra, Akshay (2016). "Current Status of the New Antiepileptic Drugs in Chronic Pain". Frontiers in Pharmacology. 7: 276. doi: 10.3389/fphar.2016.00276 . ISSN   1663-9812. PMC   4996999 . PMID   27610084.
  9. ↑ Tomić, Maja; Pecikoza, Uroš; Micov, Ana; Vučković, Sonja; Stepanović-Petrović, Radica (2018-12-01). "Antiepileptic drugs as analgesics/adjuvants in inflammatory pain: current preclinical evidence". Pharmacology & Therapeutics. 192: 42–64. doi:10.1016/j.pharmthera.2018.06.002. ISSN   0163-7258. PMID   29909236. S2CID   49291532.
  10. ↑ "DailyMed - TEGRETOL- carbamazepine suspension TEGRETOL- carbamazepine tablet TEGRETOL XR- carbamazepine tablet, extended release". dailymed.nlm.nih.gov. Retrieved 2023-11-08.
  11. ↑ Chen, Jiatong (Steven); Kandle, Patricia F.; Murray, Ian V.; Fitzgerald, Lauren A.; Sehdev, Jasjit S. (2023), "Physiology, Pain", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   30969611 , retrieved 2023-11-06
  12. ↑ "Cymbalta (duloxetine hydrochloride) capsules" (PDF). FDA Highlights of Drug Prescribing Information. 2010.
  13. ↑ "EFFEXOR XR® (venlafaxine Extended-Release) Capsules" (PDF). FDA Highlights of Prescribing Information. 2017.
  14. ↑ "Amitriptyline Hydrochloride Tablets, USP". www.accessdata.fda.gov. Retrieved 2023-11-08.
  15. 1 2 Fudin, Jeffrey; Mena, Raouf (11 April 2017). "A Review of Skeletal Muscle Relaxants for Pain Management". Practical Pain Management. 16 (5).
  16. ↑ Schoonover, Julie; Rubin, Susan E. (March 2022). "Should Muscle Relaxants Be Used as Adjuvants in Patients With Acute Low Back Pain?". American Family Physician. 105 (3): 221. ISSN   1532-0650. PMID   35289585.
  17. 1 2 Giovannitti, Joseph A.; Thoms, Sean M.; Crawford, James J. (2015). "Alpha-2 Adrenergic Receptor Agonists: A Review of Current Clinical Applications". Anesthesia Progress. 62 (1): 31–38. doi:10.2344/0003-3006-62.1.31. ISSN   0003-3006. PMC   4389556 . PMID   25849473.
  18. ↑ Kumar, Anil; Maitra, Souvik; Khanna, Puneet; Baidya, Dalim Kumar (2014). "Clonidine for management of chronic pain: A brief review of the current evidences". Saudi Journal of Anaesthesia. 8 (1): 92–96. doi: 10.4103/1658-354X.125955 . ISSN   1658-354X. PMC   3950462 . PMID   24665248.
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