drug development

Modified Botulinum Molecules Ease Pain in Mouse Models

New constructs target spinal NK1R-expressing neurons, or mu opioid receptor-containing cells, to relieve inflammatory and neuropathic pain

by Kayt Sukel on 23 Aug 2018

Comment

Botulinum toxin, a neurotoxin made by the bacterium Clostridium botulinum, inhibits neuronal signaling by blocking neurotransmitter release, leading to paralysis. Researchers from University College London (UCL), UK; the University…

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Endogenous Opioid Peptides and Non-Peptide Opioid Drugs Drive Different Patterns of Receptor Activation

Nanobody biosensor reveals that peptides activate opioid receptors first at the plasma membrane and then in endosomes, while drugs also propel activation in the Golgi apparatus

by Kayt Sukel on 16 Jul 2018

Comment

Non-peptide opioid drugs like morphine and fentanyl bind to opioid receptors (ORs) on the neuronal cell membrane, just as naturally occurring peptide OR ligands do, to bring about analgesia.…

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A Molecular Complex Within the Brain Underlies Opioid Tolerance in Rodents

Disrupting the interaction among opioid receptors, vasopressin receptors, and beta-arrestin-2 offers a potential strategy to slow tolerance in humans, though questions remain

by Matthew Soleiman on 19 Jun 2018

Comment

Patients who take opioids for chronic pain typically develop tolerance to these drugs. Now, researchers led by Taka-aki Koshimizu, Jichi Medical University, Shimotsuke, Japan, and Yukio Takano, Fukuoka University,…

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Tamper-Resistant Opioid Yields Mixed Results

New formulation of oxycodone curbs tampering among high-risk individuals but doesn’t change overall opioid use or related harm at a population level, according to a new Australian study

by Matthew Soleiman on 22 Mar 2018

Comment

Like the United States, Australia is in the midst of an opioid crisis. In response, companies in both countries have introduced versions of oxycodone that are difficult to tamper…

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The Kappa Opioid Receptor Takes Shape

Newly revealed structure of active state of KOR will aid in design of safer, more effective opioids

by Dara Bree on 28 Feb 2018

Comment

Opioids provide rapid and potent pain relief, but these drugs are associated with numerous side effects, including respiratory depression, tolerance, dependence, and addiction. Now, a new study led by…

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Lost in Translation: Without New Proteins, Chronic Pain Cannot Take Off

A first-in-class RNA decoy blocks PABP from attaching to messenger RNA, preventing translation and pain sensitization

by Nathan Fried on 21 Feb 2018

Comment

Pain sensitivity after an injury, such as damage to a nerve or an inflammatory insult, involves the synthesis of new proteins in pain neurons. This process is thought to…

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Designing Safer Opioids: How Biased Are You?

A systematic analysis of multiple mu opioid receptor agonists reveals that bias factor correlates with therapeutic window

by Nathan Fried on 11 Jan 2018

Comment

Developing safer opioids remains a long-held goal of pain researchers, who have especially set their sights on the mu opioid receptor (MOR). Agonists that bind MORs can activate multiple…

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Where Will New Pain Drugs Come From?

11th Annual Pain and Migraine Therapeutics Summit in San Diego seeks to fill the drug pipeline

by Stephani Sutherland on 6 Dec 2017

Comment

The 11th Annual Pain and Migraine Therapeutics Summit, chaired by William Schmidt, NorthStar Consulting, Davis, US, and organized by Arrowhead Publishers and Conferences was held September 27-28, 2017, in…

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An Ion Channel That Perpetuates Pain in Diabetic Neuropathy

Peripheral HCN2 lowers threshold for pain in mouse models of type 1, type 2 diabetes

by Matthew Soleiman on 27 Nov 2017

Comment

Diabetes is on the rise, and consequently, so is the persistent and often intractable pain experienced by many diabetic patients with nerve injury. However, researchers still have a poor…

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A Sound Approach to Pain Relief?

Ultrasound-triggered release of sodium channel blocker from liposomes provides on-demand local anesthesia, according to a new rat study

by Dara Bree on 13 Sep 2017

Comment

Relief of acute postoperative pain and other forms of acute pain remains a significant challenge. Up to 41 percent of patients experience moderate to severe pain after surgery—a worrying…

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Consider the Endosome: New Life for Neurokinin 1 Receptor Antagonists?

Blocking substance P activation of NK1R in endosomes is more effective at relieving pain than cell surface inhibition, but questions remain

by Nathan T. Fried on 18 Jul 2017

Comment

Troves of preclinical data initially supported a key role for substance P, a neurotransmitter released in response to painful stimuli, in chronic pain. In clinical trials, however, highly selective…

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A New Opioid Targets Active Sites of Inflammation to Relieve Pain

NFEPP binds and activates mu-opioid receptors only at low pH, soothing pain in rats without typical side effects

by Nathan T. Fried on 23 Mar 2017

Comment

Adverse effects of opioids can occur because the drugs act at both injured and healthy tissue, but if researchers could find a way to direct opioids only to the…

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A Novel Kappa Opioid Receptor Agonist May Unlock New Treatment Strategies for Pain

Biased agonism at KOR relieves pain and itch while avoiding side effects

by Hillary Doyle on 9 Jan 2017

Comment

Activation of the kappa opioid receptor (KOR) relieves pain and itch. However, downstream recruitment of β-arrestin proteins and accompanying dysphoria—a feeling of discomfort or aversion—and sedation prevent drugs targeting…

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An Opioid-like Drug Dulls Pain With Fewer Side Effects

New molecule biases µ-opioid receptor signaling toward G protein pathway

by Matthew Soleiman on 16 Sep 2016

Comment

Opioids remain a mainstay of pain therapy, but their addictive qualities and sometimes life-threatening side effects, such as respiratory depression, have fueled the search for better drugs. Now, a…

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The Long Road to Precision Pain Medicine

From gene to drug: targeting Nav1.7 mutations in inherited erythromelalgia

by Stephani Sutherland on 10 May 2016

Comment

Voltage-gated sodium channels found in sensory neurons—and the channel dubbed Nav1.7 in particular—are prime targets when it comes to developing the next generation of pain drugs. Nav1.7 is an…

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Botulinum Toxin Offers Relief From Neuropathic Pain

Clinical trial finds repeated injections are effective and safe, particularly in patients with more severe allodynia and greater nerve fiber density

by Matthew Soleiman on 7 Apr 2016

Comment

Since its initial use to treat muscle hyperactivity, botulinum toxin type A (BoNT-A), a bacterially derived toxin that blocks neurotransmitter release, has been studied for possible analgesic effects. Several…

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Will Death in French Drug Trial Lead to Tighter Phase 1 Rules?

Clinical trial of FAAH inhibitor has tragic consequences

by Madolyn Bowman Rogers on 1 Feb 2016

Comment

Editor’s note: The following was adapted, with permission, from a news story that originally appeared on the Alzforum.

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Location, Location, Location: TRPV1 Agonist Hits the Spot for Pain Relief

Computed tomography imaging aids in delivery of resiniferatoxin to ablate peripheral pain fibers and reduce thermal pain in pigs

by Matthew Soleiman on 13 Oct 2015

Comment

Current treatments for chronic pain have important limitations. For instance, opioids are the most common therapy, but they have serious side effects and carry the risk of abuse and…

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Endoplasmic Reticulum Stress Emerges as Fundamental Pain Regulator

Anti-inflammatory lipid molecules link ER stress, neuropathic pain

by Stephani Sutherland on 24 Jul 2015

Most strategies to relieve neuropathic pain are aimed at the ion channels and neurotransmitters that govern overactive electrophysiological activity of neurons. But what if earlier stages of pain signaling…

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Human “Pain-Protective Haplotype” Explained in Mouse Study

Novel inhibitor aimed at enzyme in tetrahydrobiopterin pathway reduces pain in neuropathic, inflammatory models without adverse effects

by Stephani Sutherland on 6 Jul 2015

Comment

Nearly a decade ago, researchers discovered a quirk of human genetics: people with a certain haplotype allele—found in about 15 percent of the population—of the gene for GTP cyclohydroxylase…

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Truncated Mu-Opioid Receptor Mediates Analgesia

Mouse study finds that a drug targeting MOR splice variant relieves pain without usual opioid side effects

by Allison Marin on 2 Jul 2015

Comment

Opioids are a mainstay in treating many kinds of pain but are accompanied by troubling side effects and abuse potential that limit their use. The search for opioids that…

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A New Bioelectronic Device for Pain Treatment

Experimental implant delivers GABA to spinal cord, relieves pain in rats

by Carol Cruzan Morton on 8 Jun 2015

Comment

Delivering drugs to the spinal cord, where pain signals are relayed from the peripheral nervous system ultimately up to the brain, is a desirable approach to quelling pain, but…

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Biogen Idec Announces Plans to Buy Nav1.7 Program

Convergence Pharmaceuticals’ pain candidate gets vote of confidence

by Stephani Sutherland on 26 Jan 2015

Comment

On January 11, pharmaceutical giant Biogen Idec announced that it would acquire Convergence Pharmaceuticals, a small UK company that has developed a compound aimed at alleviating neuropathic pain by…

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Repurposed Drugs Show Promise to Treat Chemotherapy-Induced Peripheral Neuropathy

Diabetes and multiple sclerosis drugs produce positive results in animal models, are poised for human testing

by Abdul-Kareem Ahmed on 12 Aug 2014

Comment

One of the most common reasons cancer patients stop chemotherapy early is because of a single side effect, chemotherapy-induced peripheral neuropathy (CIPN). Characterized by a gradual destruction of sensory…

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Pain and Depression: A Comorbidity Conundrum

News from the 2014 NIH Pain Consortium Symposium on biological and psychological factors that contribute to chronic pain

by Pat McCaffrey on 9 Jul 2014

Interest in pain is on the rise at the US National Institutes of Health (NIH), said Nora Volkow, chief of the National Institute on Drug Abuse, welcoming participants to…

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Pain and Sleep: Solve One Problem, Solve the Other?

More from the 2014 NIH Pain Consortium Symposium on biological and psychological factors that contribute to pain

by Pat McCaffrey on 9 Jul 2014

Comment

From pain and depression, the NIH Pain Consortium Symposium agenda moved to pain and sleep disorders. Michael Vitiello, University of Washington School of Medicine, Seattle, US, described results of…

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When Cancer Treatment Packs a Painful Punch

Research into chemotherapy-induced neuropathy puts focus on mitochondria, but new therapies remain elusive

by David C. Holzman on 6 Jun 2014

“It was pretty embarrassing,” said Gary Bennett of McGill University, Montreal, Canada. It was 2005, and his group had been working on a rat model of paclitaxel-induced peripheral neuropathy.…

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The Pain Treatment Pipeline: Biased Ligands, Monoclonal Antibodies, and More

7th Annual Pain and Migraine Therapeutics Summit in San Diego features diverse therapeutic approaches

by Neil Andrews on 20 Mar 2014

Comment

The West Coast edition of the 2013 Pain Therapeutics Summit, organized by Arrowhead Publishers and Conferences and chaired by William Schmidt, NorthStar Consulting, Davis, California, US, was held November…

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Toxineering: New Tool for Harnessing the Power of Nature’s Poisons

Screening approach could improve the design of ion channel-modifying drugs

by Allison Curley on 25 Feb 2014

Comment

Although spiders, snakes, and other poisonous predators get a bad rap, the diverse and highly specific peptides found in their venoms have proven quite useful for uncovering the function…

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New Possibilities for Pain Treatment

7th Annual Pain Therapeutics Summit showcases therapies in development

by Megan Talkington on 20 Feb 2014

Comment

The annual Pain Therapeutics Summit, organized by Arrowhead Publishers and Conferences and chaired by William Schmidt, NorthStar Consulting, Davis, California, US, brings together investigators from industry and academia to…

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Topical Compound Boosts Trophic Factor Actions to Stem Neuropathy

Drug restores thermal nociception in two mouse models of small fiber neuropathy

by Stephani Sutherland on 19 Feb 2014

Comment

The term small fiber neuropathy (SFN) encompasses a mixed bag of conditions with a unifying element: damage or malfunction in unmyelinated peripheral nerves. In new work from Gabriel Corfas…

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Labeling of Pills Proves Potent in Pain Relief

Clinical study quantifies effect of positive information about placebo or active drug in migraine

by Michele Solis on 18 Jan 2014

Comment

When testing drugs for pain relief, the information doctors give matters almost as much as the medicine subjects receive, according to a study published January 8 in Science Translational…

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Compound That Affects Kinase in Pain Pathway Also Targets Sodium Channels Directly

Findings presented at Neuroscience 2013 in San Diego suggest a single molecule could have a dual role in relieving pain

by Stephani Sutherland on 26 Nov 2013

Comment

Metabotropic signaling by proteins such as kinases modulates the sodium channels that drive action potential firing in pain-sensing neurons and has therefore joined the ranks of potential targets for…

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Chloride Transporter Emerges as Druggable Target for Pain

KCC2-selective compound restores impaired chloride transport in neurons and improves hypersensitivity in rat model of neuropathic pain

by Stephani Sutherland on 16 Oct 2013

Comment

The potassium-chloride cotransporter KCC2 might seem an unlikely target for the next generation of pain medications. The humble protein, found on neurons in the dorsal horn of the spinal…

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Transcranial Magnetic Stimulation: The Next Wave in Pain Treatment?

Non-invasive technique shows promise but needs more study

by Stephani Sutherland on 3 Oct 2013

Comment

Electrical stimulation of the motor cortex was established as an effective treatment for pain 20 years ago, but the risks and drawbacks of surgically implanting electrodes in the brain…

Drug Development

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A Path to Personalized Pain Treatment?

Experts say clinic-based observational studies can provide the evidence needed for rational opioid prescribing

by Megan Talkington on 5 Apr 2013

Comment

Opioids are in crisis. Many physicians and patients say that the medications can be used responsibly to treat chronic pain. Yet experts also warn that prescriptions are out of…

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Making an IMMPACT on Pain Research

A decade after its first meeting, initiative has helped clinical trials move from confusion to consensus

by Megan Talkington on 5 Mar 2013

Comment

At the 2002 World Congress on Pain, two researchers got to talking. Robert Dworkin of the University of Rochester, New York, US, and Dennis Turk of the University of…

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Filling the Pain Drug Pipeline

From small molecules to gene therapy, speakers at the Pain Therapeutics Summit in San Jose offer up diverse new approaches

by Megan Talkington on 11 Dec 2012

The 6th Annual Pain Therapeutics Summit, held 3-4 October 2012 in San Jose, California, US, and organized by Arrowhead Publishers and Conferences, brought together approximately 100 researchers from industry…

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Trial Tribulations: The Challenges of Testing New Pain Treatments

Speakers at the Pain Therapeutics Summit in San Jose take on design and conduct of analgesic trials

by Megan Talkington on 13 Nov 2012

Comment

The 6th Annual Pain Therapeutics Summit, held 3-4 October in San Jose, California, US, and organized by Arrowhead Publishers and Conferences, brought together approximately 100 researchers from industry and…

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Epigenetic Targets in Pain

News from Milan and the IASP 2012 World Congress on Pain

by Neil Andrews on 11 Oct 2012

Comment

From August 27-31, pain researchers and clinicians from around the world gathered in Milan, Italy, for the 14th World Congress on Pain. With more than 7,700 attendees, the Congress…

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NGF Update: Antibodies Get a Second Chance and Small Molecules Zero In on TrkA

News from Milan and the IASP 2012 World Congress on Pain

by Pat McCaffrey on 2 Oct 2012

Comment

From August 27-31, pain researchers and clinicians from around the world gathered in Milan, Italy, for the 14th World Congress on Pain. With more than 7,700 attendees, the Congress…

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A New Twist on Treating Chronic Bladder Pain

Pretzel-shaped lidocaine-releasing device shows promising results in women with interstitial cystitis/bladder pain syndrome

by Sonya Jakawich on 16 Aug 2012

Targeted drug delivery offers the hope of teaching old dogs new tricks, repurposing existing treatments by deploying them to previously inaccessible sites of pain. In a paper published July…

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Database Offers Snapshot of Pain Clinical Trials

RReACTing to elusive outcomes data

by Megan Talkington on 8 Aug 2012

Comment

Researchers seeking clinical trial data on particular drugs or conditions can check online registries such as the US National Institutes of Health (NIH)’s ClinicalTrials.gov, but the information they find…

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FDA Advisory Panel Gives the Green Light to Restart NGF Antibody Trials

Investigators pleased that promising agents for pain relief have new life

by Megan Talkington on 13 Mar 2012

Comment

An advisory panel of the U.S. Food and Drug Administration (FDA) has voted unanimously that antibodies against nerve growth factor (NGF) should re-enter clinical trials for pain. The 21-person…

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News Brief: Decision Day Approaches for NGF Antibodies

FDA advisory committee to decide fate of halted development program

by Megan Talkington on 9 Mar 2012

Comment

Antibodies inhibiting nerve growth factor (NGF) are profoundly effective pain relievers in clinical trials, and, if approved, would become the first new class of analgesics for osteoarthritis, and possibly…

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Rodent, Heal Thyself

Study suggests rats self-medicate with a CB2 agonist to relieve pain

by Megan Talkington on 19 May 2011

In animal models, measuring responses to evoked pain is relatively straightforward, but it is a formidable challenge to figure out whether an animal is in pain, and whether an…

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Taking Aim at Pain in the Brain

The anterior cingulate cortex may hold new drug targets for chronic pain

by Megan Talkington on 31 Mar 2011

How does chronic pain start? Many researchers now believe the bulk of the blame falls on the brain. But how can we make the pain stop? When it comes…

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The IASP Pain Research Forum is a publication of the International Association for the Study of Pain