Editing Analgesic (section)

== Classification ==
Analgesics are typically classified based on their mechanism of action.<ref>{{Cite web|url=https://www.medicinescomplete.com/mc/bnf/current/PHP78520-analgesics.htm?q=Painkillers&t=search&ss=text&tot=2&p=2#_hit|title=British National Formulary: Analgesics|website=BNF online|access-date=8 June 2017}}</ref>

[[File:Tylenol.jpg|thumb|left|A bottle of [[acetaminophen]]|182x182px]]

=== Paracetamol (acetaminophen) ===
{{main|Paracetamol}}
Paracetamol, also known as acetaminophen or APAP, is a medication used to treat [[pain]] and [[fever]].<ref name="AHFS2016">{{cite web|title=Acetaminophen|url=https://www.drugs.com/monograph/acetaminophen.html|publisher=The American Society of Health-System Pharmacists|url-status=live|archive-url=https://web.archive.org/web/20160605063136/http://www.drugs.com/monograph/acetaminophen.html|archive-date=2016-06-05}}</ref> It is typically used for mild to moderate pain.<ref name="AHFS2016" /> In combination with [[opioid analgesic|opioid pain medication]], paracetamol is now used for more severe pain such as [[cancer pain]] and after surgery.<ref>{{cite book|chapter-url = http://www.sign.ac.uk/pdf/SIGN106.pdf|title = Guideline 106: Control of pain in adults with cancer|author = Scottish Intercollegiate Guidelines Network (SIGN)|publisher = National Health Service (NHS)|location = Scotland|year = 2008|isbn = 9781905813384|chapter = 6.1 and 7.1.1|url-status = live|archive-url = https://web.archive.org/web/20101220061154/http://sign.ac.uk/pdf/SIGN106.pdf|archive-date = 2010-12-20}}</ref> It is typically used either by mouth or [[rectally]] but is also available [[intravenously]].<ref name="AHFS2016" /><ref name="Hoch2014" /> Effects last between two and four hours.<ref name="Hoch2014" /> Paracetamol is classified as a mild analgesic.<ref name="Hoch2014">{{cite book | vauthors = Hochhauser D |title = Cancer and its Management |date=2014 |publisher=John Wiley & Sons |isbn=9781118468715 |page=119 |url= https://books.google.com/books?id=CXjDBAAAQBAJ&pg=PA119 |url-status=live|archive-url=https://web.archive.org/web/20170910083948/https://books.google.co.jp/books?id=CXjDBAAAQBAJ&pg=PA119|archive-date=2017-09-10|author-link=Daniel Hochhauser}}</ref> Paracetamol is generally safe at recommended doses.<ref>{{cite journal | vauthors = Russell FM, Shann F, Curtis N, Mulholland K | title = Evidence on the use of paracetamol in febrile children | journal = Bulletin of the World Health Organization | volume = 81 | issue = 5 | pages = 367–72 | date = 2003 | pmid = 12856055 | pmc = 2572451 }}</ref>

===NSAIDs===
{{main|Nonsteroidal anti-inflammatory drug}}
Nonsteroidal anti-inflammatory drugs (usually abbreviated to NSAIDs), are a [[drug class]] that groups together [[drug]]s that decrease pain<ref name="researchgate.net">{{cite journal | vauthors = Mallinson T |title=A review of ketorolac as a prehospital analgesic |journal=Journal of Paramedic Practice |date=2017 |volume=9 |issue=12 |pages=522–526 |url=https://www.researchgate.net/publication/321640488 |access-date=2 June 2018 |language=en|doi=10.12968/jpar.2017.9.12.522 |doi-access=free }}</ref> and [[antipyretic|lower fever]], and, in higher doses, decrease [[inflammation]].<ref name="Mallinson">{{cite journal | vauthors = Mallinson T |title=A review of ketorolac as a prehospital analgesic |journal=Journal of Paramedic Practice |date=2017 |volume=9 |issue=12 |pages=522–526 |url=https://www.researchgate.net/publication/321640488 |access-date=2 June 2018 |publisher=MA Healthcare |location=London |language=en |url-status=live |archive-url=https://web.archive.org/web/20180605033254/https://www.researchgate.net/publication/321640488_A_review_of_ketorolac_as_a_prehospital_analgesic |archive-date=5 June 2018 |doi=10.12968/jpar.2017.9.12.522 |doi-access=free }}</ref> The most prominent members of this group of drugs—[[aspirin]], [[ibuprofen]] and [[naproxen]], and [[diclofenac]] are all available [[Over-the-counter drug|over the counter]] in most countries.<ref name="The Physician and Sportsmedicine 2010">{{cite journal | vauthors = Warden SJ | title = Prophylactic use of NSAIDs by athletes: a risk/benefit assessment | journal = The Physician and Sportsmedicine | volume = 38 | issue = 1 | pages = 132–8 | date = April 2010 | pmid = 20424410 | doi = 10.3810/psm.2010.04.1770 | url = http://www.physsportsmed.com/index.php?article=1770 | url-status = live | s2cid = 44567896 | archive-url = https://web.archive.org/web/20101126145938/http://physsportsmed.com/index.php?article=1770 | archive-date = 2010-11-26 }}</ref>

==== COX-2 inhibitors ====
{{Main|COX-2 inhibitor}}

These drugs have been derived from NSAIDs. The [[cyclooxygenase]] enzyme inhibited by NSAIDs was discovered to have at least two different versions: COX1 and COX2. Research suggested most of the adverse effects of NSAIDs to be mediated by blocking the COX1 ([[Constitutive enzyme|constitutive]]) enzyme, with the analgesic effects being mediated by the COX2 ([[Adaptive enzyme|inducible]]) enzyme. Thus, the COX2 inhibitors were developed to inhibit only the COX2 enzyme (traditional NSAIDs block both versions in general). These drugs (such as [[rofecoxib]], [[celecoxib]], and [[etoricoxib]]) are equally effective analgesics when compared with NSAIDs, but cause less gastrointestinal hemorrhage in particular.<ref name="Conaghan2012">{{cite journal | vauthors = Conaghan PG | title = A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology, comparative efficacy, and toxicity | journal = Rheumatology International | volume = 32 | issue = 6 | pages = 1491–502 | date = June 2012 | pmid = 22193214 | pmc = 3364420 | doi = 10.1007/s00296-011-2263-6 }}</ref>

After widespread adoption of the COX-2 inhibitors, it was discovered that most of the drugs in this class increase the risk of [[cardiovascular event]]s by 40% on average. This led to the withdrawal of rofecoxib and valdecoxib, and warnings on others. Etoricoxib seems relatively safe, with the risk of [[thrombotic]] events similar to that of non-coxib NSAID diclofenac.<ref name="Conaghan2012" />

=== Opioids ===
{{Main|Opioid}}

[[Morphine]], the archetypal [[opioid]], and other opioids (e.g., [[codeine]], [[oxycodone]], [[hydrocodone]], [[dihydromorphine]], [[pethidine]]) all exert a similar influence on the [[Cerebrum|cerebral]] [[opioid receptor]] system. [[Buprenorphine]] is a [[partial agonist]] of the μ-opioid receptor, and [[tramadol]] is a serotonin norepinephrine reuptake inhibitor (SNRI) with weak μ-opioid receptor agonist properties.<ref>{{cite journal | vauthors = Smith HS, Raffa RB, Pergolizzi JV, Taylor R, Tallarida RJ | title = Combining opioid and adrenergic mechanisms for chronic pain | journal = Postgraduate Medicine | volume = 126 | issue = 4 | pages = 98–114 | date = July 2014 | pmid = 25141248 | doi = 10.3810/pgm.2014.07.2788 | s2cid = 19782818 }}</ref> [[Tramadol]] is structurally closer to [[venlafaxine]] than to [[codeine]] and delivers analgesia by not only delivering "opioid-like" effects (through mild agonism of the [[mu receptor]]) but also by acting as a weak but fast-acting [[serotonin releasing agent]] and [[norepinephrine reuptake inhibitor]].<ref name="pmid1596676">{{cite journal | vauthors = Driessen B, Reimann W | title = Interaction of the central analgesic, tramadol, with the uptake and release of 5-hydroxytryptamine in the rat brain in vitro | journal = British Journal of Pharmacology | volume = 105 | issue = 1 | pages = 147–51 | date = January 1992 | pmid = 1596676 | pmc = 1908625 | doi = 10.1111/j.1476-5381.1992.tb14226.x }}</ref><ref name="pmid9389855">{{cite journal | vauthors = Bamigbade TA, Davidson C, Langford RM, Stamford JA | title = Actions of tramadol, its enantiomers and principal metabolite, O-desmethyltramadol, on serotonin (5-HT) efflux and uptake in the rat dorsal raphe nucleus | journal = British Journal of Anaesthesia | volume = 79 | issue = 3 | pages = 352–6 | date = September 1997 | pmid = 9389855 | doi = 10.1093/bja/79.3.352 | doi-access = free }}</ref><ref name="pmid9671098">{{cite journal | vauthors = Reimann W, Schneider F | title = Induction of 5-hydroxytryptamine release by tramadol, fenfluramine and reserpine | journal = European Journal of Pharmacology | volume = 349 | issue = 2–3 | pages = 199–203 | date = May 1998 | pmid = 9671098 | doi = 10.1016/S0014-2999(98)00195-2 }}</ref><ref name="pmid12354291">{{cite journal | vauthors = Gobbi M, Moia M, Pirona L, Ceglia I, Reyes-Parada M, Scorza C, Mennini T | title = p-Methylthioamphetamine and 1-(m-chlorophenyl)piperazine, two non-neurotoxic 5-HT releasers in vivo, differ from neurotoxic amphetamine derivatives in their mode of action at 5-HT nerve endings in vitro | journal = Journal of Neurochemistry | volume = 82 | issue = 6 | pages = 1435–43 | date = September 2002 | pmid = 12354291 | doi = 10.1046/j.1471-4159.2002.01073.x | hdl = 10533/173421 | s2cid = 13397864 | hdl-access = free }}</ref> [[Tapentadol]], with some structural similarities to tramadol, presents what is believed to be a novel drug working through two (and possibly three) different modes of action in the fashion of both a traditional opioid and as an SNRI. The effects of serotonin and [[norepinephrine reuptake inhibitor|norepinephrine]] on pain, while not completely understood, have had causal links established and drugs in the SNRI class are commonly used in conjunction with opioids (especially tapentadol and tramadol) with greater success in pain relief.

Dosing of all opioids may be limited by opioid toxicity (confusion, respiratory depression, [[myoclonus|myoclonic jerks]] and pinpoint pupils), seizures ([[tramadol]]), but opioid-tolerant individuals usually have higher dose ceilings than patients without tolerance.<ref>{{cite web| vauthors = Tozer A |title=Replacing Opioids: Developing drugs to treat pain|url=https://www.analyticalcannabis.com/articles/replacing-opioids-developing-drugs-to-treat-pain-289925|website=Analytical Cannabis|access-date=22 August 2017|url-status=live|archive-url=https://web.archive.org/web/20170822182648/https://www.analyticalcannabis.com/articles/replacing-opioids-developing-drugs-to-treat-pain-289925|archive-date=22 August 2017}}</ref>
Opioids, while very effective analgesics, may have some unpleasant side-effects. Patients starting morphine may experience [[nausea]] and [[vomiting]] (generally relieved by a short course of [[antiemetic]]s such as [[phenergan]]). [[Pruritus]] (itching) may require switching to a different opioid. [[Constipation]] occurs in almost all patients on opioids, and [[laxative]]s ([[lactulose]], [[macrogol]]-containing or co-danthramer) are typically co-prescribed.<ref name="oxford">Oxford Textbook of Palliative Medicine, 3rd ed. (Doyle D, Hanks G, Cherney I and Calman K, eds. Oxford University Press, 2004).</ref>

When used appropriately, opioids and other central analgesics are safe and effective; however, risks such as addiction and the body's becoming used to the drug (tolerance) can occur. The effect of tolerance means that frequent use of the drug may result in its diminished effect. When safe to do so, the dosage may need to be increased to maintain effectiveness against tolerance, which may be of particular concern regarding patients with chronic pain and requiring an analgesic over long periods. Opioid tolerance is often addressed with [[opioid rotation|opioid rotation therapy]] in which a patient is routinely switched between two or more non-cross-tolerant opioid medications in order to prevent exceeding safe dosages in the attempt to achieve an adequate analgesic effect.

Opioid tolerance should not be confused with [[opioid-induced hyperalgesia]]. The symptoms of these two conditions can appear very similar but the mechanism of action is different. Opioid-induced hyperalgesia is when exposure to opioids increases the sensation of pain ([[hyperalgesia]]) and can even make non-painful stimuli painful ([[allodynia]]).<ref>{{cite journal | vauthors = Bannister K | title = Opioid-induced hyperalgesia: where are we now? | journal = Current Opinion in Supportive and Palliative Care | volume = 9 | issue = 2 | pages = 116–21 | date = June 2015 | pmid = 25872113 | doi = 10.1097/SPC.0000000000000137 | s2cid = 13922218 }}</ref>

===Alcohol===
{{see also|Ethanol}}
Alcohol has biological, mental, and social effects which influence the consequences of using alcohol for pain.<ref name="ZaleMaisto2015">{{cite journal | vauthors = Zale EL, Maisto SA, Ditre JW | title = Interrelations between pain and alcohol: An integrative review | journal = Clinical Psychology Review | volume = 37 | pages = 57–71 | date = April 2015 | pmid = 25766100 | pmc = 4385458 | doi = 10.1016/j.cpr.2015.02.005 }}</ref> Moderate use of alcohol can lessen certain types of pain in certain circumstances.<ref name="ZaleMaisto2015" />

The majority of its analgesic effects come from antagonizing NMDA receptors, similarly to ketamine, thus decreasing the activity of the primary excitatory (signal boosting) [[neurotransmitter]], glutamate. It also functions as an analgesic to a lesser degree by increasing the activity of the primary inhibitory (signal reducing) neurotransmitter, GABA.<ref>{{cite journal | vauthors = Nagy J | title = Alcohol related changes in regulation of NMDA receptor functions | journal = Current Neuropharmacology | volume = 6 | issue = 1 | pages = 39–54 | date = March 2008 | pmid = 19305787 | pmc = 2645546 | doi = 10.2174/157015908783769662 }}</ref>

Attempting to use alcohol to treat pain has also been observed to lead to negative outcomes including excessive drinking and [[alcohol use disorder]].<ref name="ZaleMaisto2015" />

===Cannabis===
{{main|Medical cannabis}}
''Medical cannabis'', or ''medical marijuana'', refers to [[Cannabis (drug)|cannabis]] or its [[cannabinoids]] used to treat disease or improve symptoms.<ref>{{cite journal | vauthors = Murnion B | title = Medicinal cannabis | journal = Australian Prescriber | volume = 38 | issue = 6 | pages = 212–5 | date = December 2015 | pmid = 26843715 | pmc = 4674028 | doi = 10.18773/austprescr.2015.072 }}</ref><ref>{{cite web|title=What is medical marijuana?|url=https://www.drugabuse.gov/publications/drugfacts/marijuana-medicine|website=National Institute of Drug Abuse|access-date=19 April 2016|date=July 2015|quote=The term medical marijuana refers to using the whole unprocessed marijuana plant or its basic extracts to treat a disease or symptom.|url-status=live|archive-url=https://web.archive.org/web/20160417154854/https://www.drugabuse.gov/publications/drugfacts/marijuana-medicine|archive-date=17 April 2016}}</ref> There is evidence suggesting that cannabis can be used to treat [[chronic pain]] and [[muscle spasms]], with some trials indicating improved relief of neuropathic pain over opioids.<ref name="Borgelt2013">{{cite journal | vauthors = Borgelt LM, Franson KL, Nussbaum AM, Wang GS | s2cid = 8503107 | title = The pharmacologic and clinical effects of medical cannabis | journal = Pharmacotherapy | volume = 33 | issue = 2 | pages = 195–209 | date = February 2013 | pmid = 23386598 | doi = 10.1002/phar.1187 | doi-access = free }}</ref><ref name="JAMA2015">{{cite journal | vauthors = Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, Keurentjes JC, Lang S, Misso K, Ryder S, Schmidlkofer S, Westwood M, Kleijnen J | display-authors = 6 | title = Cannabinoids for Medical Use: A Systematic Review and Meta-analysis | journal = JAMA | volume = 313 | issue = 24 | pages = 2456–73 | date = 23 June 2015 | pmid = 26103030 | doi = 10.1001/jama.2015.6358 | url = http://jama.jamanetwork.com/data/journals/jama/934167/joi150059.pdf | url-status = live | archive-url = https://web.archive.org/web/20170921232733/http://jama.jamanetwork.com/data/journals/jama/934167/joi150059.pdf | archive-date = 21 September 2017 | hdl = 10757/558499 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Jensen B, Chen J, Furnish T, Wallace M | title = Medical Marijuana and Chronic Pain: a Review of Basic Science and Clinical Evidence | journal = Current Pain and Headache Reports | volume = 19 | issue = 10 | pages = 50 | date = October 2015 | pmid = 26325482 | doi = 10.1007/s11916-015-0524-x | s2cid = 9110606 }}</ref>

=== Combinations ===

Analgesics are frequently used in combination, such as the [[paracetamol]] and [[codeine]] preparations found in many non-prescription pain relievers. They can also be found in combination with vasoconstrictor drugs such as [[pseudoephedrine]] for [[Paranasal sinus|sinus]]-related preparations, or with [[antihistamine]] drugs for people with allergies.

While the use of paracetamol, aspirin, [[ibuprofen]], [[naproxen]], and other [[NSAIDS]] concurrently with weak to mid-range opiates (up to about the hydrocodone level) has been said to show beneficial synergistic effects by combating pain at multiple sites of action,<ref name="pmid34636261">{{cite journal | vauthors = Patel R, Dickenson AH | title = Neuropharmacological basis for multimodal analgesia in chronic pain | journal = Postgraduate Medicine  | volume = 134| issue = 3| pages = 245–259 | date = October 2021 | pmid = 34636261 | doi = 10.1080/00325481.2021.1985351 | s2cid = 238635838 }}</ref><ref name="pmid12148679">{{cite journal | vauthors = Mehlisch DR | title = The efficacy of combination analgesic therapy in relieving dental pain | journal = Journal of the American Dental Association | volume = 133 | issue = 7 | pages = 861–71 | date = July 2002 | pmid = 12148679 | doi = 10.14219/jada.archive.2002.0300 }}</ref> several combination analgesic products have been shown to have few efficacy benefits when compared to similar doses of their individual components. Moreover, these combination analgesics can often result in significant adverse events, including accidental overdoses, most often due to confusion that arises from the multiple (and often non-acting) components of these combinations.<ref name="nps01">{{cite journal | vauthors = Murnion B |title=Combination analgesics in adults |journal=Australian Prescriber |issue=33 |pages=113–5 |url=http://www.australianprescriber.com/magazine/33/4/113/5 |access-date=12 August 2010 |url-status=usurped |archive-url=https://web.archive.org/web/20120325192249/http://www.australianprescriber.com/magazine/33/4/113/5 |archive-date=25 March 2012 }}</ref>

===Alternative medicine===
There is some evidence that some treatments using alternative medicine can relieve some types of pain more effectively than [[placebo]].<ref name="alternative medicine reviews">*{{cite journal | vauthors = Oltean H, Robbins C, van Tulder MW, Berman BM, Bombardier C, Gagnier JJ | s2cid = 4498929 | title = Herbal medicine for low-back pain | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD004504 | date = December 2014 | volume = 2014 | pmid = 25536022 | doi = 10.1002/14651858.CD004504.pub4 | pmc = 7197042 }}
* {{cite journal | vauthors = Cameron M, Gagnier JJ, Chrubasik S | title = Herbal therapy for treating rheumatoid arthritis | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD002948 | date = February 2011 | pmid = 21328257 | doi = 10.1002/14651858.CD002948.pub2 }}
* {{cite journal | vauthors = Cui X, Trinh K, Wang YJ | title = Chinese herbal medicine for chronic neck pain due to cervical degenerative disc disease | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD006556 | date = January 2010 | volume = 2010 | pmid = 20091597 | doi = 10.1002/14651858.CD006556.pub2 | pmc = 7389878 }}</ref> The available research concludes that more research would be necessary to better understand the use of alternative medicine.<ref name="alternative medicine reviews" />

=== Other drugs ===
[[Nefopam]]—a monoamine reuptake inhibitor, and calcium and sodium channel modulator—is also approved for the treatment of moderate to severe pain in some countries.<ref>{{cite journal | vauthors = Girard P, Chauvin M, Verleye M | title = Nefopam analgesia and its role in multimodal analgesia: A review of preclinical and clinical studies | journal = Clinical and Experimental Pharmacology & Physiology | volume = 43 | issue = 1 | pages = 3–12 | date = January 2016 | pmid = 26475417 | doi = 10.1111/1440-1681.12506 | doi-access = free }}</ref>

[[Flupirtine]] is a centrally acting K<sup>+</sup> channel opener with weak [[NMDA antagonist]] properties.<ref>{{cite journal | vauthors = Kornhuber J, Bleich S, Wiltfang J, Maler M, Parsons CG | title = Flupirtine shows functional NMDA receptor antagonism by enhancing Mg2+ block via activation of voltage independent potassium channels. Rapid communication | journal = Journal of Neural Transmission | volume = 106 | issue = 9–10 | pages = 857–67 | year = 1999 | pmid = 10599868 | doi = 10.1007/s007020050206 | s2cid = 11636934 }}</ref> It was used in Europe for moderate to strong pain, as well as its [[migraine]]-treating and muscle-relaxant properties. It has no significant [[anticholinergic]] properties, and is believed to be devoid of any activity on dopamine, serotonin, or histamine receptors. It is not addictive, and tolerance usually does not develop.<ref>{{cite journal | vauthors = Klawe C, Maschke M | title = Flupirtine: pharmacology and clinical applications of a nonopioid analgesic and potentially neuroprotective compound | journal = Expert Opinion on Pharmacotherapy | volume = 10 | issue = 9 | pages = 1495–500 | date = June 2009 | pmid = 19505216 | doi = 10.1517/14656560902988528 | s2cid = 11597721 }}</ref> However, tolerance may develop in some cases.<ref>{{cite journal | vauthors = Stoessel C, Heberlein A, Hillemacher T, Bleich S, Kornhuber J | title = Positive reinforcing effects of flupirtine--two case reports | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 34 | issue = 6 | pages = 1120–1 | date = August 2010 | pmid = 20362025 | doi = 10.1016/j.pnpbp.2010.03.031 | s2cid = 19710997 }}</ref>

[[Ziconotide]], a blocker of potent [[N-type calcium channel|N-type voltage-gated calcium channels]], is administered [[intrathecally]] for the relief of severe, usually cancer-related pain.<ref>{{cite journal | vauthors = Bäckryd E | title = Do the potential benefits outweigh the risks? An update on the use of ziconotide in clinical practice | journal = European Journal of Pain | volume = 22 | issue = 7 | pages = 1193–1202 | date = August 2018 | pmid = 29635804 | doi = 10.1002/ejp.1229 | url = http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-149838 | s2cid = 4710528 }}</ref>

=== Adjuvants ===
{{Main|Analgesic adjuvant}}
Certain drugs that have been introduced for uses other than analgesics are also used in pain management. Both first-generation (such as [[amitriptyline]]) and newer [[Serotonin–norepinephrine reuptake inhibitor|antidepressants]] (such as [[duloxetine]]) are used alongside NSAIDs and opioids for pain involving nerve damage and similar problems. Other agents directly potentiate the effects of analgesics, such as using [[hydroxyzine]], [[promethazine]], [[carisoprodol]], or [[tripelennamine]] to increase the pain-killing ability of a given dose of opioid analgesic.

Adjuvant analgesics, also called atypical analgesics, include [[orphenadrine]], [[mexiletine]], [[pregabalin]], [[gabapentin]], [[cyclobenzaprine]], [[hyoscine]] (scopolamine), and other drugs possessing anticonvulsant, anticholinergic, and/or antispasmodic properties, as well as many other drugs with CNS actions. These drugs are used along with analgesics to modulate and/or modify the action of opioids when used against pain, especially of neuropathic origin.

[[Dextromethorphan]] has been noted to slow the development of and reverse tolerance to opioids, as well as to exert additional analgesia by acting upon [[NMDA]] receptors, as does [[ketamine]].<ref>{{cite journal | vauthors = Hewitt DJ | title = The use of NMDA-receptor antagonists in the treatment of chronic pain | journal = The Clinical Journal of Pain | volume = 16 | issue = 2 Suppl | pages = S73-9 | date = June 2000 | pmid = 10870744 | doi = 10.1097/00002508-200006001-00013 | s2cid = 40067641 }}</ref> Some analgesics such as [[methadone]] and [[ketobemidone]] and perhaps [[piritramide]] have intrinsic NMDA action.<ref>{{cite journal | vauthors = Elliott KJ, Brodsky M, Hyanansky A, Foley KM, Inturrisi CE | title = Dextromethorphan shows efficacy in experimental pain (nociception) and opioid tolerance | journal = Neurology | volume = 45 | issue = 12 Suppl 8 | pages = S66-8 | date = December 1995 | pmid = 8545027 | doi = 10.1212/WNL.45.12_Suppl_8.S66 | publisher = NEUROLOGY, 2005 | s2cid = 46279174 }}</ref>

The [[anticonvulsant]] [[carbamazepine]] is used to treat neuropathic pain. Similarly, the [[gabapentinoid]]s [[gabapentin]] and [[pregabalin]] are prescribed for neuropathic pain, and [[phenibut]] is available without prescription. Gabapentinoids work as α<sub>2</sub>δ-subunit blockers of [[voltage-gated calcium channel]]s, and tend to have other mechanisms of action as well. Gabapentinoids are all [[anticonvulsant]]s, which are most commonly used for neuropathic pain, as their mechanism of action tends to inhibit pain sensation originating from the nervous system.<ref>{{cite book|title=Drug Treatment in Urology|publisher=John Wiley & Sons, 2008| vauthors  = Eardley I, Whelan P, Kirby R, Schaeffer A |page=65|chapter=Drugs Used In The Treatment Of Interstitial Cystitis}}</ref>

=== Other uses ===

Topical analgesia is generally recommended to avoid systemic side-effects. Painful joints, for example, may be treated with an [[ibuprofen]]- or [[diclofenac]]-containing gel (The labeling for topical diclofenac has been updated to warn about drug-induced hepatotoxicity.<ref>[https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm Voltaren Gel (diclofenac sodium topical gel) 1% – Hepatic Effects Labeling Changes<!-- Bot generated title -->] {{webarchive|url=https://web.archive.org/web/20140108173957/https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm |date=2014-01-08 }}</ref>); [[capsaicin]] also is used [[topical cream|topical]]ly. [[Lidocaine]], an [[anesthetic]], and [[glucocorticoid|steroids]] may be injected into joints for longer-term pain relief. Lidocaine is also used for painful [[mouth sore]]s and to numb areas for [[dentistry|dental]] work and minor medical procedures. In February 2007 the FDA notified consumers and healthcare professionals of the potential hazards of topical anesthetics entering the bloodstream when applied in large doses to the skin without medical supervision. These topical anesthetics contain anesthetic drugs such as lidocaine, tetracaine, benzocaine, and prilocaine in a cream, ointment, or gel.<ref>[https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm054718.htm] {{webarchive|url=https://web.archive.org/web/20101019055341/https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm054718.htm|date=October 19, 2010}}</ref>