[1] Various analgesics, such as many NSAIDs, are available over the counter in most countries, whereas various others are prescription drugs owing to the substantial risks and high chances of overdose, misuse, and addiction in the absence of medical supervision.

The word analgesic derives from Greek an- (ἀν-, "without"), álgos (ἄλγος, "pain"),[2] and -ikos (-ικος, forming adjectives).

[15][16][17][18] 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.

[20] 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.

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.

[22] 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.

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,[29][30] several combination analgesic products have been shown to have few efficacy benefits when compared to similar doses of their individual components.

[32] 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.

[36] Ziconotide, a blocker of potent N-type voltage-gated calcium channels, is administered intrathecally for the relief of severe, usually cancer-related pain.

Both first-generation (such as amitriptyline) and newer antidepressants (such as duloxetine) are used alongside NSAIDs and opioids for pain involving nerve damage and similar problems.

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.

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.

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.

[42] Topical nonsteroidal anti-inflammatory drugs provide pain relief in common conditions such as muscle sprains and overuse injuries.

[43] Some novel and investigational analgesics include subtype-selective voltage-gated sodium channel blockers such as funapide and raxatrigine, as well as multimodal agents such as ralfinamide.