Understanding Opportunities for Non-Invasive Pain Treatments
An effective therapeutic treatment for acute or chronic pain needs to be convenient, easy to self-administer, and have rapid onset to provide fast relief.
Pain management involves a multimodal approach that consists of using treatments from one or more clinical disciplines incorporated into an overall treatment plan. This plan allows for different approaches to address the pain condition (acute and/or chronic) and may include medication, restorative therapies, interventional procedures, behavioral health approaches, and complementary and integrative health.
Part of the chronic pain treatment paradigm is pharmacotherapy and there are numerous classes of pain medications (for example, non-steroidal anti-inflammatory drugs, anxiolytics, and opioids) available dependent on the condition, its severity, and other factors. In general, oral administration is a convenient and effective dosing route to control chronic pain.
Acute pain is a fact of life for everyone at one time or another. It can occur after a trauma or following surgery and may also be experienced with underlying medical conditions, such as migraine, neuropathies, neuralgia, and multiple sclerosis. In these instances, an effective therapeutic treatment needs to be convenient, easy to self-administer, and have rapid onset to provide fast relief.
Rapid Treatment for Rapid Onset Pain
Rapid onset usually entails parenteral administration, typically intravenous. Therapeutic blood levels are quickly obtained, and the pain is effectively managed. The problem with the parenteral route of administration is the need for a health care professional to administer the drug.
This typically occurs in an emergency department (ED) or similar health care setting. In other settings, including those encountered by emergency responders dealing with severe trauma, parenteral administration can also be challenging.
Thus, there is a significant unmet need for alternative treatment paradigms for acute pain that would mitigate some of the challenges of current treatment options both inside the medical setting and out in the community.
Intranasal delivery of pain medications is an attractive alternative to current modalities and for acute pain, it can be categorized as a rescue treatment where rapid onset and ease of use are paramount.
Intranasal Delivery: Pros and Cons
Intranasal delivery frequently presents challenges for the formulator with respect to drug loading and bioavailability. There are physiological constraints with respect to dose volume and residence time in the nose that must be overcome to produce an effective nasal drug product.
Numerous strategies can be applied to overcome these challenges, notably improving bioavailability by the incorporation of an absorption enhancer. This has the benefit of reducing the amount of drug required to achieve systemic therapeutic levels, thus reducing the solubility burden while increasing the absorption rate.
Intranasal delivery is gaining traction as an alternative treatment modality for rescue medications. Rescue therapies can be defined as therapies in which rapid onset to achieve therapeutic drug levels is of overriding importance to the overall treatment paradigm.
This is exemplified by naloxone nasal spray (Narcan) which is used to treat opiate-induced respiratory depression and/or central nervous system depression. Clearly, rapid onset is fundamental to the efficacy of this product with the potential for patient death by respiratory failure if not immediately treated.
Another intranasal rescue treatment, approved by the FDA in 2020, is diazepam nasal spray (Valtoco), which is indicated for the treatment of acute repetitive seizures in patients with epilepsy, 6 years of age and older. Again, rapid onset is a fundamental requirement for seizure control, which may mitigate potential neurological damage. In the pain space specifically, treatments that address acute migraine using nasal spray formulations of sumatriptan have become viable options as well.
In both examples, a second important aspect is ease of use. These products can be self-administered or used by a parent or other care partner with no specific training required other than following the instructions for use that accompany the medication.
These products are also portable and easily carried in a purse, backpack, or pocket so they are at hand should the need arise. This convenience and ease of use also extends to the ED and the emergency response settings, greatly facilitating prompt patient treatment and management.
Nasal sprays are very familiar delivery devices to the general population, with OTC products available as nasal sprays delivering antihistamines and corticosteroids for nasal decongestion and similar applications.Nasal sprays come in various configurations with single-use and multiple-use options depending on the treatment regimen. Rescue medications typically come in single-use devices.
Nasal sprays are classified and regulated as medical devices and, as such, must meet rigorous regulatory standards covering their design, manufacture, and performance. Part of these standards include human factor studies designed to assess the device’s ease of use and the patient or care partner’s ability to follow the instructions for use before administering the correct dose.
These studies provide significant assurance to regulators that the device is easy to use and the instructions are clear and easy to follow. Providing guidance to first-time users of nasal sprays is therefore relatively straightforward, whether this is by the physician, nurse, or pharmacist.
Non-invasive nasal delivery methods hold a lot of promise for pain treatment. Broader awareness and availability of these treatments could change how we approach treating acute pain and, in particular, conditions in which patients often struggle to find rapid, effective relief, such as migraines.
About the Author
Stuart Madden, PHD, CCHEM, FRSC, Chief Scientific Officer at Neurelis, Inc.