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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

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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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Highlights From the 2017 Annual Meeting of the American Pain Society: Part 2

At the Basic Science SIG dinner, rigor, bias, and transparency in science were the main course

by by Stephani Sutherland on 17 Jul 2017

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Editor’s note: The following is Part 2 of a two-part report on selected presentations from the 36th Annual Scientific Meeting of the American Pain Society (APS), held May 17-20, 2017,…

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How Cancer Hides Pain

PD-L1 signals through its receptor PD-1 on sensory neurons, suppresses pain in melanoma-bearing mice

by Matthew Soleiman on 5 Jul 2017

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Cancer is often painful, but some types, such as melanomas and glioblastomas, are notably pain-free. Now, Ru-Rong Ji, Duke University, Durham, US, and colleagues might have found one reason…

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Highlights From the 2017 Annual Meeting of the American Pain Society: Part 1

Nutrition, inflammation, and pain: how diet cranks pain up—and dials it down

by Stephani Sutherland on 26 Jun 2017

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Editor’s note: The following is Part 1 of a two-part report on selected presentations from the 36th Annual Scientific Meeting of the American Pain Society (APS), held May 17-20,…

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A New Brain Measure of Nociception in Infants

EEG recordings reveal noxious-evoked brain activity that can serve as an objective measure of pain and analgesic efficacy

by Nathan Fried on 12 Jun 2017

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Unlike adults, infants can’t tell you if they’re in pain. Instead, clinicians must interpret behaviors such as crying and physiological measures such as heart rate to determine what a…

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The Mysterious Link Between Migraine Aura and Headache

New MRI study finds no evidence for a weakened blood-brain barrier in migraine with aura patients

by Matthew Soleiman on 31 May 2017

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For decades, researchers have wondered if migraine attacks are somehow tied to the blood-brain barrier. According to one hypothesis, a wave of decreased activity in the cortex, known as…

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To (Not) Sleep, Perchance to Feel More Pain?

New mouse study links decreased alertness from sleep loss to increased pain sensitivity, lack of analgesic efficacy

by Neil Andrews on 24 May 2017

Sleep. Everyone needs it, but not everyone gets it—at least not enough of it. Now, new animal research builds the case that a lack of sleep has significant and…

Research

GABA in the Dorsal Root Ganglia Blunts Pain in Rats

Local activity of neurotransmitter in DRG could serve as early “gate” for pain signals

by Matthew Soleiman on 1 May 2017

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Pain signals, once they are triggered, are thought to travel largely uninterrupted from the skin and other tissues into the spinal cord, where they are first filtered. But now,…

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Long-Term Neuropathic Pain Leads to Changes in Gene Expression in Brain Areas Associated With Depression

RNA sequencing in multiple connected brain regions identifies large number of genes underlying pain-depression connection; new study will serve as resource for future work

by Nathan Fried on 19 Apr 2017

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Over half of all chronic pain patients also develop depression. Researchers know that short-term pain affects brain areas implicated in depression, but few studies have scrutinized the effects of…

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Itch in the Periphery, Pain in the Spinal Cord: The Dual Nature of MRGPRX1

Activation of G protein-coupled receptor in central terminals dampens pain in “humanized” mice

by Stephani Sutherland on 6 Apr 2017

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MRGPRX1, a human mas-related G protein-coupled receptor (MRGPR), detects itchy stimuli in the skin. But in new research, MRGPRX1 activation in the spinal cord dampens pain in mice, confirming…

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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

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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 Subset of Spinal Interneurons Triggers Intensity-Dependent Itch and Pain

New “leaky gate” model helps explain how the two sensations are encoded in mice

by Matthew Soleiman on 15 Mar 2017

Itch and pain have a complicated relationship. Pain can suppress itch, and yet itch seldom suppresses pain; in fact, some itchy substances also cause mild pain. Now, researchers led…

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For Pain, Green Light Means Stop

Visual exposure to green light is analgesic in rats

by Stephani Sutherland on 6 Mar 2017

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The next big wave in pain treatment might come in the form of light waves—green light, in particular. No, not from a high-tech optogenetic manipulation, but simply ambient green…

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Inhibition of Pannexin-1 Channels on Microglia Reduces Morphine Withdrawal in Rodents

Findings point the way toward a clinical strategy to mitigate an adverse effect of opioids

by Nathan Fried on 21 Feb 2017

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Opioids are the mainstay of treatment strategies to reduce pain, but withdrawal can be a serious problem when patients stop taking these drugs. However, beyond the recognition that microglia…

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Mu-Opioid Receptors on Nociceptors, Not Microglia, Drive Morphine Tolerance and Hyperalgesia in Mice

New findings suggest a possible strategy to curb opioid side effects in patients while maintaining analgesia

by Matthew Soleiman on 16 Feb 2017

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Researchers have long sought to minimize the side effects of opioids without sacrificing the unparalleled analgesia they offer. Now, Grégory Scherrer, Stanford University, US, and colleagues show that it’s…

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Highlights From Neuroscience 2016: Part 3

Machine learning finds brain activity differs in low and high pain states during chronic low back pain

by Stephani Sutherland on 13 Feb 2017

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Editor’s Note: The 2016 annual meeting of the Society for Neuroscience took place November 12-16, 2016, in San Diego, US. Part 3, below, of our coverage of the meeting is…

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Highlights From Neuroscience 2016: Part 2

New compound boosts endogenous cannabinoids to alleviate pain

by Stephani Sutherland on 6 Feb 2017

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Editor’s Note: The 2016 annual meeting of the Society for Neuroscience took place November 12-16, 2016, in San Diego, US. Part 2, below, of our coverage of the meeting…

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Highlights From Neuroscience 2016: Part 1

David Julius delivers sweeping history of thermosensors in featured lecture at Society for Neuroscience annual meeting

by Stephani Sutherland on 31 Jan 2017

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Editor’s Note: The 2016 annual meeting of the Society for Neuroscience took place November 12-16, 2016, in San Diego, US. Part 1, below, of our coverage of the meeting…

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A Small Molecule Takes the Pain Out of Touch

Researchers identify an inhibitor of STOML3 that reverses mechanical hypersensitivity in mice

by Matthew Soleiman on 23 Jan 2017

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A nerve injury can render even the softest touch painful. This hypersensitivity, known as tactile allodynia, stems in part from the actions of stomatin-like protein-3 (STOML3), a protein that’s…

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A Bright Future for Brain Imaging of Pain

In plenary talk at IASP World Congress on Pain, Irene Tracey emphasized translational potential of neuroimaging research

by Katherine Martucci on 17 Jan 2017

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Irene Tracey, University of Oxford, UK, summarized the contributions of neuroimaging to pain research, and directions for future investigations, during “Translating Neuroimaging Discovery Science for Patient Benefit,” a plenary…

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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

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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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Autism Gene Modulates Thermal Pain

SHANK3, a gene closely associated with autism spectrum disorders, regulates TRPV1 function, possibly contributing to changes in pain sensitivity seen in autism

Nathan Fried on 4 Jan 2017

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Autism spectrum disorders (ASDs) are most often described in terms of their associated cognitive, social, and communication deficits, but ASDs are also characterized by extensive changes to sensory perception,…

Research

Most DRG Sensory Neurons Are Modality-Specific, Not Polymodal

In vivo calcium imaging in mice illuminates long-standing question in the field

by Allison Marin on 26 Dec 2016

The use of genetically encoded calcium indicators in vivo reveals polymodality is a rare phenomenon in dorsal root ganglion (DRG) sensory neurons. Instead, most of these neurons respond specifically…

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PRF’s Top News Stories and Papers of the Week for 2016

News covering precision pain medicine, and a paper on a new technique to visualize populations of DRG neurons, come out on top

by PRF Team on 19 Dec 2016

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The new year—2017!—is almost here, so it’s a good time to review the most popular news articles and papers from the past year on PRF. We used Google Analytics to…

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A New Form of Synaptic Plasticity in Pain Pathways

Glial cells trigger long-term potentiation at active, and inactive, synapses in the spinal cord of rats

by Matthew Soleiman on 12 Dec 2016

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Chronic pain is thought to involve the long-lasting strengthening of synapses, akin to what happens during the formation of new memories. This phenomenon, known as long-term potentiation (LTP), is…

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From the Gut to the Brain and Back Again: The Importance of the Microbiome in Visceral Pain

Plenary lecture by John Cryan at 2016 World Congress on Pain described the role of the gut microbiota in pain responses

by Genevieve D’souza on 5 Dec 2016

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Editor’s note: The International Association for the Study of Pain’s 16th World Congress on Pain took place from September 26-30, 2016, in Yokohama, Japan. Nearly 4,500 pain researchers and clinicians…

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Meeting Report: Virtual Reality Pain 2016

New technology opens virtual world for pain treatment

by Stephani Sutherland on 29 Nov 2016

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When Dave Thomas initially talked to people at the National Institutes of Health (NIH) about funding research on virtual reality (VR) back in 2004, most were skeptical or dismissive.…

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DREADD Inhibition of Nociceptors: Interpret Results With Caution

Chemogenetic technique to produce analgesia in mice also disrupts endogenous signaling

by Allison Marin on 21 Nov 2016

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The designer receptors exclusively activated by designer drugs (DREADD) system can be used to suppress nociceptors, resulting in analgesia to heat, reports a new mouse study. But thanks to…

Research

Olfactory Cues Facilitate the Social Transfer of Pain in Mice

Control animals housed in same room but different cage as experimental animals experience pain hypersensitivity

by Nathan Fried on 9 Nov 2016

Social influences can profoundly modulate pain in both humans and rodents. A handful of studies have shown that when two animals experience the same pain stimulus while housed together,…

Research

Why Do Naked Mole-Rats Show an Absence of Pain Sensitization?

Tweaks to TrkA, a nerve growth factor receptor, explain lack of heat hyperalgesia in the animals

by Matthew Soleiman on 3 Nov 2016

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The naked mole-rat is not your typical rodent. It’s cold-blooded, lives for decades, and does not experience certain forms of pain. Now, researchers led by Gary Lewin, Max Delbrück…

Research

Patients With PIEZO2 Mutations Show Deficits in Mechanosensation and Proprioception

Results parallel findings from knockout mice, but the transducer of human mechanical pain remains unknown

by Hillary Doyle on 17 Oct 2016

Comment

Mechanosensation—the ability to sense force—is a fundamental sensory process in people and other animals. However, while researchers have made progress in identifying molecular mechanisms of mechanosensation in animal studies,…

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Novel Imaging Technique Reveals Coupled Activation of Primary Sensory Neurons After Nerve Injury

Neuron-to-neuron coupling, and neuron-to-satellite glia coupling, both occur in the dorsal root ganglion during chronic pain; role for gap junctions identified

by Hillary Doyle on 20 Sep 2016

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Primary sensory neurons in the dorsal root ganglion (DRG) are responsible for transmission of pain signals from the periphery to the spinal cord. Sensitization of these neurons through tissue…

Research

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

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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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Is It Time to Deprioritize Preclinical Pain Research?

At the North American Pain School, trainees debated the pros and cons of the issue

by Nathan Fried on 13 Sep 2016

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Editor’s Note:The first-ever North American Pain School (NAPS) took place June 26-30, 2016, in Montebello, Quebec, Canada. An educational initiative of the International Association for the Study of Pain (IASP);…

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Dialogue, Dialogue, Dialogue: Strategies to Facilitate Translation

The development of new and effective analgesics requires ongoing, productive, back-and-forth communication between basic scientists and clinicians

by Ram Kandasamy on 30 Aug 2016

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Editor’s Note: The first-ever North American Pain School (NAPS) took place June 26-30, 2016, in Montebello, Quebec, Canada. An educational initiative of the International Association for the Study of Pain…

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Spinal Cord Neurons Encode Heat and Cold in Different Ways

Mouse neurons represent absolute temperature for heat, change in temperature for cold

by Matthew Soleiman on 26 Aug 2016

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Our sense of temperature can tell us whether an environment is hospitable or harmful. Researchers have spent over half a century deciphering how nerve fibers in the skin represent…

Research

Overcoming the “Valleys of Death”: Strategies to Make Research Have Impact After Publication

Pain researchers are using social media platforms to disseminate new findings and increase research translation

by Erinn Acland on 8 Aug 2016

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Editor’s Note: The first-ever North American Pain School (NAPS) took place June 26-30, 2016, in Montebello, Quebec, Canada. An educational initiative of the International Association for the Study of Pain…

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The Two Faces of Adenosine

Long recognized as an analgesic when acting through its A1 receptor, adenosine also contributes to chronic pain through its A2B receptor and subsequent neuroimmune signaling

by Matthew Soleiman on 26 Jul 2016

Comment

Over several decades, adenosine—a purine nucleoside involved in many physiological and pathophysiological processes—has gained a reputation as a molecule that relieves pain. But there have also been scattered reports…

Research

Spinal Cord Circuitry: Wired for Allodynia

A recent PRF webinar examined dorsal horn mechanisms contributing to neuropathic pain

by Stephani Sutherland on 21 Jul 2016

Comment

Allodynia is a hallmark of neuropathic pain in which normally non-painful stimuli, such as a light touch, evoke pain. Researchers have recently taken strides toward understanding the neuronal circuitry…

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Highlights From the 2016 Annual Scientific Meeting of the American Pain Society: Part 3

How plasticity creates a “pain biography”

by Stephani Sutherland on 28 Jun 2016

The following is Part 3 of a three-part series of selected presentations from the 35th Annual Scientific Meeting of the American Pain Society (APS) held May 11-14, 2016, in…

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Highlights From the 2016 Annual Scientific Meeting of the American Pain Society: Part 2

APS Basic Science Shared Interest Group Dinner and Town Hall Discussion: Animal Models and Testing in Preclinical Pain Research

by Stephani Sutherland on 14 Jun 2016

The following is Part 2 of a three-part series of selected presentations from the 35th Annual Scientific Meeting of the American Pain Society (APS) held May 11-14, 2016, in…

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Research

Leaving a Mark: Changes in the Epigenome During Chronic Pain

Nerve injury produces molecular footprints in spinal cord microglia in an animal model, possibly priming the cells for subsequent pain

by Matthew Soleiman on 6 Jun 2016

Comment

Why pain persists well after a nerve injury has taken place remains a key question for pain researchers. The enduring aspect of chronic pain suggests that lasting changes in…

Research

Highlights From the 2016 Annual Scientific Meeting of the American Pain Society: Part 1

Exercise may protect against subsequent neuropathic pain

by Stephani Sutherland on 26 May 2016

Comment

The following is Part 1 of a three-part series of selected presentations from the 35th Annual Scientific Meeting of the American Pain Society (APS) held May 11-14, 2016, in…

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Tracking the Natural History of Small Fiber Neuropathy

Longitudinal, case-control study points to the rate of intraepidermal nerve fiber loss as a possible diagnostic measure

by Matthew Soleiman on 18 May 2016

Comment

In small fiber neuropathy (SFN), the degeneration of thinly myelinated and unmyelinated sensory axons is associated with symptoms such as pain, tingling, and numbness. In diagnosing the condition, clinicians…

Research

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…

Drug Development

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Kinase Inhibition Improves Neuropathic Pain in Mice

Knockout of WNK1 splice variant implicated in human disorder protects animals from pain, via effects on potassium-chloride co-transporter, restoration of GABA inhibitory action

by Allison Marin on 4 May 2016

Comment

The WNK1/HSN2 kinase, mutated in a hereditary form of pain insensitivity, contributes to neuropathic pain and is a potential new target for analgesic drugs, reports a new mouse study.

Research

Mindfulness Effective for Chronic Low Back Pain in Clinical Trial

A second study hints at how mindfulness reduces acute pain

by Stephani Sutherland on 15 Apr 2016

Comment

Government officials, physicians, and the public are increasingly aware of a need to move away from using opiate drugs to treat chronic pain. More and more, doctors are searching…

Research

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…

Drug Development

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Tiny Population of Oxytocin Neurons Controls Analgesia in Rats

Activation of parvocellular oxytocin neurons in the hypothalamus improves inflammatory pain

by Allison Marin on 31 Mar 2016

Comment

A new study identifies a very small population of about 30 specialized parvocellular oxytocin (OT) neurons that project simultaneously to the supraoptic nucleus (SON) of the hypothalamus and to…

Research

Peripheral Afferent Drive Reduced in Chronic Inflammatory Pain

Differences also emerge between young and aged mice

by Stephani Sutherland on 14 Mar 2016

Comment

A major question facing the pain field remains: Is chronic pain maintained by changes in the central nervous system (CNS) alone, or does primary afferent nerve input contribute? Now,…

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