**7. Conclusions**

NSAIDs have been used historically to treat both acute and chronic pain. They possess analgesic, antipyretic, and anti-inflammatory properties through the inhibition of the pro-inflammatory cyclooxygenase (COX) enzymes. Their mechanism of action allows them to establish efficacy in treating a variety of pain diseases but also allows their routine use to produce serious side effects. COX-1 receptors are expressed throughout our body and its inhibition can lead to gastric mucosal injury including gastroduodenal ulcers. Selective COX-2 inhibitors were created with hopes of avoiding the side effects connected with non-selective COX-inhibitors; however, they are associated with their own complications which include an increased risk for cardiovascular events (thrombosis and hypertension).

Opioids remain a popular option in treating pain due to their effect on the Mu (μ), Delta (δ), and Kappa (κ) receptors. By activating these receptors, opioids can prevent the release of pain-promoting neurotransmitters providing their analgesic effects. However, the activation of the same receptors is also responsible for the associated side effects. These side effects vary depending on either acute or chronic use but can be life-threatening in some cases. This includes respiratory depression which can lead to fatal apnea. Chronic opioid use is associated with opioid induced constipation that can cause significant morbidity. It is therefore recommended to include prophylactic laxatives with chronic regimens. It is important to remember that addiction and tolerance is associated with opioid use due to its euphoric effect. Therefore, the clinical use of these medications should not only depend on their mechanism of action but also on understanding the potential severe complications that arise with their use.

Neuropathic chronic pain disorders have been effectively treated with antidepressants. These disorders include, but are not limited to, diabetic peripheral neuropathy, HIV polyneuropathy, and post-herpetic neuralgia. One of the first line options are the tricyclic antidepressants (TCAs) which are usually started and maintained at lower doses versus the depression doses. This helps reduce some of their side effects including urinary retention, sedation, and dry mouth. Other antidepressants include serotonin-norepinephrine reuptake inhibitors that are also used in the management of neuropathic disorders.

Cannabinoids exhibit their effects by binding to CB1 and CB2 receptors, two isotypes of G-protein coupled receptors. The agonism of these receptors is responsible for cannabinoids' anti-inflammatory and analgesic effects. CB1 receptor agonism is also predominately responsible for the psychoactive effect. Preclinical evidence supports anti-nociceptive effects and with recent legalization of cannabis, the use of cannabinoids to treat pain disorders will expand with ongoing research.

Ketamine has many uses in treating both acute and chronic pain including fibromyalgia. It is also used for conscious sedation due to both its dissociative and amnestic properties. Ketamine has multiple sites of interactions but it exhibits its principle nociceptive effect by acting as a non-competitive antagonist of the N-Methyl-D-Aspartate (NDMA) receptor.
