Tag Archives: opioid

Months after an injury has healed, receptors involved in modulating pain remain active

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shutterstock_139125542Pain researchers know that, in the immediate aftermath of a severe injury, pain sensitization pathways become active, causing the body to produce opioids—naturally occurring chemicals that inhibit pain by activating receptors. But a mouse study published today in Science reveals that a specific type of opioid receptor found on the surface of nerve cells remains hyperactive months after an injury has healed—a period much longer than previously thought. Moreover, blocking this receptor from binding opioids can produce opioid withdrawal, much like that experienced by people addicted to heroin or codeine. This finding suggests that opioids only serve to mask underlying pain, shedding light on why some chronic nature of pain disorders.

To study the long-term role of ‘endogenous’ opioids produced naturally by the body, scientists created an inflammatory response in the paws of mice by injecting a dose of toxic bacteria fragments. The researchers then allowed the injury to heal for a period of three weeks or more, all the while monitoring how sensitive the area was by using molecular biomarkers and recording how often the rodents made facial grimaces or withdrew their paws when the injured area was touched.

Six months on, once the injury had healed, the researchers administered naltrexone methobromide, a drug that blocks the receptors that can normally bind to opioids. Surprisingly, blocking the receptor’s activity caused the pain to return, even though considerable time had passed. Moreover, the mice also exhibited the telltale signs of opioid withdrawal, such as jumping, shaking and teeth chattering. “We think it’s possible that the body becomes dependent on the endogenous opioid system after an injury,” says neurobiologist and co-author Bradley Taylor, of the University of Kentucky in Lexington, “but this is speculative.” If these results are further validated, this could be the first recorded expression of what the researchers call ‘endogenous opioid withdrawal’.

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Better labeling aimed to spur development of abuse-resistant painkillers

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Prescription opioid pain relievers such as codeine and oxycodone are among the most widely abused drugs in the US. The country’s Centers for Disease Control and Prevention (CDC) estimated that in 2010 around 12 million Americans aged 12 or older used this class of drugs for nonmedical purposes, at a cost of up to $72.5 billion in direct healthcare expenses. Worse, the CDC estimates that around 15,000 fatalities occur each year due to overdoses from these meds, a number comparable to the total number of annual murders nationwide.

In response to this growing public health crisis, the US Food and Drug Administration (FDA) yesterday released a draft guidance detailing how the agency plans to evaluate new opioid pain relievers with special formulations designed to reduce abuse. Importantly, it gave pharmaceutical companies labeling guidelines.

“Our goal here is to encourage the development of abuse deterrent formulations that work to reduce abuse in the real world, in the community. The intent of this guidance is to incentivize that, to encourage the development of that science,” said Douglas Throckmorton, deputy director of the FDA’s Center for Drug Evaluation and Research, in a conference call to reporters.

Drugs with abuse-deterrent properties have already been developed and sold on the market. For example, Endo Pharmaceuticals of Chadds Ford, Pennsylvania, sells a tablet called Opana ER that releases its active painkilling ingredient slowly over time and is harder to abuse by crushing or snorting. But Endo is not allowed to include any permutation of the term “abuse-deterrent” on the drug’s label, a major issue for a company that’s trying to differentiate its product from the pharmacopeia of other painkillers. Last year, Endo went so far as to sue the FDA to prevent a generic version of their drug’s older, non-abuse-deterrent formulation from entering the market. The generic was ultimately approved, but the timing and language of yesterday’s draft guidance should help mitigate some of the concerns raised by Endo going forward.

Despite the added clarity for drugmakers, questions remain for the health care industry as to whether doctors will ultimately prescribe the abuse-resistant painkillers, not to mention whether health insurers and patients will be willing to pay for their higher premiums next to the cheaper generic—and tamperable—alternatives.

Nathaniel Katz, president of Analgesic Solutions, a Massachusetts-based consulting firm, believes there are obvious incentives. “[Doctors] want to always prescribe the safer product,” he says. For health insurers, “from a pure financial perspective, prescription opioid abuse is a huge problem. They will increasingly recognize that, and recognize there’s a financial return on investment.”

That just leaves patients. Many people seeking pain relief, especially those who do not identify as at-risk for abuse issues, will probably not accept higher co-pays when much cheaper but abusable options are still available. Katz sees a simple solution to that problem: “Eventually the idea is perhaps that the option will no longer be available to them,” he says. As yet, however, the FDA hasn’t taken that option off the table.

Image: Ondřej Karlík, Wikimedia Commons