analgesic adjuvant

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.{{cite journal |last1=Morgan |first1=Michael M |last2=Christie |first2=MacDonald J |date=October 2011 |title=Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human |journal=British Journal of Pharmacology |language=en |volume=164 |issue=4 |pages=1322–1334 |doi=10.1111/j.1476-5381.2011.01335.x |issn=0007-1188 |pmc=3229764 |pmid=21434879}}{{cite journal |last1=Kaye |first1=AlanDavid |last2=Urman |first2=RichardD |last3=Rappaport |first3=Yury |last4=Siddaiah |first4=Harish |last5=Cornett |first5=ElyseM |last6=Belani |first6=Kumar |last7=Salinas |first7=OrlandoJ |last8=Fox |first8=CharlesJ |date=2019 |title=Multimodal analgesia as an essential part of enhanced recovery protocols in the ambulatory settings |journal=Journal of Anaesthesiology Clinical Pharmacology |language=en |volume=35 |issue=5 |pages=S40–S45 |doi=10.4103/joacp.JOACP_51_18 |issn=0970-9185 |pmc=6515722 |pmid=31142958 |doi-access=free }}{{cite journal |last1=Olmos |first1=Andrea V. |last2=Steen |first2=Sasha |last3=Boscardin |first3=Christy K. |last4=Chang |first4=Joyce M. |last5=Manahan |first5=Genevieve |last6=Little |first6=Anthony R. |last7=Lee |first7=Man-Cheung |last8=Liu |first8=Linda L. |date=2021-07-01 |title=Increasing the use of multimodal analgesia during adult surgery in a tertiary academic anaesthesia department |url=https://bmjopenquality.bmj.com/content/10/3/e001320 |journal=BMJ Open Quality |language=en |volume=10 |issue=3 |pages=e001320 |doi=10.1136/bmjoq-2020-001320 |issn=2399-6641 |pmid=34281910|pmc=8291327 }}

Anticonvulsants work through blockade of sodium and calcium ion channels to reduce glutamate (excitatory neurotransmitter) release.{{cite journal |last1=Kammerer |first1=M. |last2=Rassner |first2=M. P. |last3=Freiman |first3=T. M. |last4=Feuerstein |first4=T. J. |date=July 2011 |title=Effects of antiepileptic drugs on GABA release from rat and human neocortical synaptosomes |url=http://link.springer.com/10.1007/s00210-011-0636-8 |journal=Naunyn-Schmiedeberg's Archives of Pharmacology |language=en |volume=384 |issue=1 |pages=47–57 |doi=10.1007/s00210-011-0636-8 |issn=0028-1298 |pmid=21533993 |s2cid=1388805}} 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).{{cite journal |last1=Sidhu |first1=Harpreet S. |last2=Sadhotra |first2=Akshay |date=2016 |title=Current Status of the New Antiepileptic Drugs in Chronic Pain |journal=Frontiers in Pharmacology |volume=7 |page=276 |doi=10.3389/fphar.2016.00276 |issn=1663-9812 |pmc=4996999 |pmid=27610084 |doi-access=free}} 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.{{cite journal |last1=Tomić |first1=Maja |last2=Pecikoza |first2=Uroš |last3=Micov |first3=Ana |last4=Vučković |first4=Sonja |last5=Stepanović-Petrović |first5=Radica |date=2018-12-01 |title=Antiepileptic drugs as analgesics/adjuvants in inflammatory pain: current preclinical evidence |url=https://www.sciencedirect.com/science/article/pii/S0163725818301049 |journal=Pharmacology & Therapeutics |volume=192 |pages=42–64 |doi=10.1016/j.pharmthera.2018.06.002 |issn=0163-7258 |pmid=29909236 |s2cid=49291532}}

• Examples:
• Gabapentin
• Pregabalin
• Carbamazepine: FDA-approved for trigeminal neuralgia{{cite web |title=DailyMed - TEGRETOL- carbamazepine suspension TEGRETOL- carbamazepine tablet TEGRETOL XR- carbamazepine tablet, extended release |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8d409411-aa9f-4f3a-a52c-fbcb0c3ec053 |access-date=2023-11-08 |website=dailymed.nlm.nih.gov}}

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.{{Citation |last1=Chen |first1=Jiatong (Steven) |title=Physiology, Pain |date=2023 |url=http://www.ncbi.nlm.nih.gov/books/NBK539789/ |work=StatPearls |access-date=2023-11-06 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30969611 |last2=Kandle |first2=Patricia F. |last3=Murray |first3=Ian V. |last4=Fitzgerald |first4=Lauren A. |last5=Sehdev |first5=Jasjit S.}} 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).{{cite web |date=2010 |title=Cymbalta (duloxetine hydrochloride) capsules |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022516lbl.pdf |access-date= |website=FDA Highlights of Drug Prescribing Information}}{{cite web |date=2017 |title=EFFEXOR XR® (venlafaxine Extended-Release) Capsules |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020699s107lbl.pdf |website=FDA Highlights of Prescribing Information}}{{cite web |title=Amitriptyline Hydrochloride Tablets, USP |url=https://www.accessdata.fda.gov/spl/data/0f12f50f-7087-46e7-a2e6-356b4c566c9f/0f12f50f-7087-46e7-a2e6-356b4c566c9f.xml |access-date=2023-11-08 |website=www.accessdata.fda.gov}}

• Examples:
• Duloxetine
• Venlafaxine
• Amitriptyline

Over-excitation of skeletal muscle can result in spasticity (increased muscle tone) and/or muscle spasms (involuntary muscle contractions) which may contribute to pain.{{cite journal |last1=Fudin |first1=Jeffrey |last2=Mena |first2=Raouf |title=A Review of Skeletal Muscle Relaxants for Pain Management |url=https://www.practicalpainmanagement.com/treatments/pharmacological/non-opioids/review-skeletal-muscle-relaxants-pain-management |journal=Practical Pain Management |date=11 April 2017 |volume=16 |issue=5}} 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.{{cite journal |last1=Schoonover |first1=Julie |last2=Rubin |first2=Susan E. |date=March 2022 |title=Should Muscle Relaxants Be Used as Adjuvants in Patients With Acute Low Back Pain? |url=https://www.aafp.org/pubs/afp/issues/2022/0300/p221.html |journal=American Family Physician |language=en-US |volume=105 |issue=3 |pages=221 |issn=1532-0650 |pmid=35289585}}

• Examples:
• Cyclobenzaprine
• Methocarbamol
• Tizanidine
• Baclofen
• Carisoprodol: also active centrally and reduces perception of pain
• Diazepam

Alpha-2 adrenergic agonists such as clonidine are traditionally used to treat hypertension via inhibition of norepinephrine release.{{cite journal |last1=Giovannitti |first1=Joseph A. |last2=Thoms |first2=Sean M. |last3=Crawford |first3=James J. |date=2015 |title=Alpha-2 Adrenergic Receptor Agonists: A Review of Current Clinical Applications |journal=Anesthesia Progress |volume=62 |issue=1 |pages=31–38 |doi=10.2344/0003-3006-62.1.31 |issn=0003-3006 |pmc=4389556 |pmid=25849473}} Central alpha-2 adrenergic activation in the locus ceruleus and spinal cord induce sedation and pain modulation respectively. Clonidine has been shown to have some efficacy when treating both acute and chronic pain.{{cite journal |last1=Kumar |first1=Anil |last2=Maitra |first2=Souvik |last3=Khanna |first3=Puneet |last4=Baidya |first4=Dalim Kumar |date=2014 |title=Clonidine for management of chronic pain: A brief review of the current evidences |journal=Saudi Journal of Anaesthesia |volume=8 |issue=1 |pages=92–96 |doi=10.4103/1658-354X.125955 |issn=1658-354X |pmc=3950462 |pmid=24665248 |doi-access=free}}

• Examples:
• Clonidine
• Tizanidine: also considered a muscle relaxant

{{reflist|2}}

{{wiktionary|adjuvant}}

• [https://web.archive.org/web/20130419040358/http://apps.who.int/iris/bitstream/10665/44540/1/9789241548120_Guidelines.pdf WHO Guidelines on the Pharmacological Treatment of Persisting Pain in Children with Medical Illnesses], (2012), World Health Organization

{{Analgesics}}

{{Pain}}

Category:Nociception

Category:Sensory systems

Category:Suffering

Category:Acute pain

Category:Analgesics

Category:Adjuvants