A brief Introduction

Aspadol is a generic version of the brand medication Tapentadol. It is used to relieve acute and chronic pain disorders and is available in immediate relief and extended-release versions. To better understand its pharmacological rationale, it is vital to have an idea about pain and the mechanism of action of Aspadol on pain.

IASP (International Association for Study of Pain) defined pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage and described in terms of such damage. Pain can be either Acute or temporary or chronic that is constant or intermittent with a longer time span. Chronic pain presents as a shooting or stabbing sensation when caused due to nerves damage and is called Neuropathic pain or present as a throbbing sensation due to damage to body tissue termed nociceptive pain.

Analgesic and Their Classification

Analgesic medications are a class of drugs that work on the brain receptors to relieve pain without loss of consciousness. NSAIDs Adjuvant (selected) analgesics are the two important classifications of the medications. Aspadol belongs to the third category of opioid analgesic that works on the dual mode of action as an agonist against the mu-opioid receptors as well as a nor-epinephrine inhibitor. Working on the nor-epinephrine inhibitor increases the levels of adrenaline that help fight the symptoms of pain and the depressive effects associated with long-term pain. The mu-opioid receptors agonist effects of Aspadol lead to comparatively very less euphoria associated with Tapentadol, thus decreasing its abuse potential and further increasing its safety.

Mu-opioid Receptors role in Pain

Mu-receptors are a class of receptors that neuro-modulate different physiological functions of the body. Pain or nociception is the most important function modulated by them. Still, they also work on other factors like stress, temperature, endocrine activity, and gastrointestinal activities with memory, mood, and motivation. Opioids on binding to the mu-receptors induce analgesic effects by regulating the pre and postsynaptic neurons. At the presynaptic neurons, MOR ( Mu Opioid Receptors) Voltage-gated calcium channels. This blocks their influx and results in lower intracellular calcium, which inhibits excitatory neurotransmitter release from the presynaptic vesicles. Similarly, activation of MOR on postsynaptic vesicles causes efflux of potassium channels. The end result is inhibition of neuronal firing and a decrease in the perception of pain.

Abuse Potential

Opioid analgesics always have a high risk of abuse potential owing to their morphine or opioid content. But Aspadol, with its unique properties, is an exception. Its dual synergistic effects also lead to increasing safety as a medication. In a study conducted to find out the abuse potential of Tapentadol, the brand version of Aspadol, 1,13,914 subjects were examined for abuse potential of the medication in comparison to other Schedule II analgesics like Tramadol, Oxycodone, Fentanyl, Hydromorphone, and Morphine. Tapentadol abuse was observed to be the least among other substances both in its immediate-release and extended-release versions.

In another study to view the efficacy of extended-release branded Aspadol, patients with moderate to severe chronic osteoarthritis, low back pain, and pain related to diabetic peripheral neuropathy were treated with an extended-release version of the medication and its comparator Oxycodone. Aspadol ER was associated with an improved tolerability profile and lower incidence of side effects, particularly gastrointestinal ones. There were also lower rates of treatment discontinuations and adverse event discontinuations, thus proving that Aspadol can be used for the long-term management of chronic pain.

Conclusion

Aspadol is a unique class of analgesic agents developed for chronic pain disorders that don't respond well to other painkillers. Its synergistic MOR-NRI action of the compound helps in the pathophysiology of chronic pain by helping in its tolerability level. Aspadol has the potential to be patients in nociceptive, neuropathic, and mixed pain to a greater degree than other opioid painkillers. More research needs to be conducted about the compound to spread awareness regarding its therapeutic effects.