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It is also important to remember that the antinociceptive responses measured in the analgesia tolerance assays involve a complex circuit response that could be affected by β- arrestin knockout at multiple sites between MOR and the motor response and that deletion of β- arrestin may affect agonist efficacy in this assay in ways that would not be evident by simply recording percent maximal possible effect

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Pharmacologic options: Antidepressants (TCAs and SNRIs) Anticonvulsants Opioids NSAIDs and Acetaminophen Naltrexone Antidepressants Tricyclic antidepressants (TCAs) Serotonin and norepinephrine help mediate descending inhibition to decrease sensory input from the periphery