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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…

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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

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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…

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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

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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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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

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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…

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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

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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

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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…

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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

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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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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

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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.

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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

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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…

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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

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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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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

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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…

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Peripheral Afferent Drive Reduced in Chronic Inflammatory Pain

Differences also emerge between young and aged mice

by Stephani Sutherland on 14 Mar 2016

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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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Stress Regulation Gene Drives Development and Maintenance of Chronic Pain in Mice

Blocking FKBP51 modulates glucocorticoid signaling to reduce mechanical hypersensitivity

by Allison Marin on 2 Mar 2016

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Spinal FKBP51, a gene known to play a role in the brain’s stress response, is important for the development and maintenance of chronic pain, reports a new mouse study…

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Exploiting Opioid Receptor Variants for Safer Analgesics

A recent PRF webinar examined the effects of mu-opioid receptor gene splicing on analgesic and off-target effects of drugs

by Stephani Sutherland on 22 Feb 2016

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Patients respond differently—and unpredictably—to opioid drugs in terms of efficacy and side effects; these individual variations arise from genetic differences. Although the drugs act at the mu-opioid receptor (MOR),…

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A New Role for a Chemokine in Neuropathic Pain

Spinal CXCL13 acts via its receptor, CXCR5, to directly activate astrocytes, leading to mechanical and thermal pain sensitivity in mice

by Matthew Soleiman on 9 Feb 2016

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During neuropathic pain, sensory neurons in the spinal cord communicate with surrounding glial cells, including astrocytes and microglia. A number of chemokines are well recognized to contribute to this…

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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

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

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Cytokine CSF1 Identified as a Key Signal From Injured Sensory Neurons to Microglia

CSF1 released from dorsal root ganglion neurons induces microglial activation and mechanical hypersensitivity in mouse model of neuropathic pain

by Allison Marin on 12 Jan 2016

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Microglial activation has long been implicated in neuropathic pain, but the signal from injured sensory neurons that prompts this response has remained elusive—until now. Researchers led by Zhonghui Guan,…

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Autoimmunity May Help Explain Chronic Pain of Rheumatoid Arthritis

Autoantibodies from RA patients administered to mice cause pain-like behavior, independent of inflammation, through chemokine signaling

by Matthew Soleiman on 4 Jan 2016

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Joint inflammation is a hallmark of rheumatoid arthritis (RA) and causes pain, yet joint pain is commonly observed before signs of inflammation become evident. Now, researchers led by Camilla…

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Pain in the ACC

A commentary on Lieberman and Eisenberger, 2015

by Tor Wager on 23 Dec 2015

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The dorsal anterior cingulate cortex (dACC) is widely regarded as a processing nexus for effortful cognitive operations and affective states, including pain. Meta-analyses of the dACC (Shackman et al. 2011;…

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Ion Channel Mutation Identified in Family With Rare Cold-Aggravated Pain

Evidence accumulates for role of voltage-gated sodium channel Nav1.9 in cold pain

by Stephani Sutherland on 21 Dec 2015

Rare, inherited pain disorders remain largely mysterious, but researchers continue to identify genetic mutations in voltage-gated sodium channels (Nav) that may give rise to them. Now, Enrico Leipold, Ingo…

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What Caught Your Eye This Year? PRF’s Top News Stories and Papers of the Week for 2015

News covering the pain-anxiety connection, and a paper offering a meta-analysis of pharmacological treatments for neuropathic pain are the winners

by PRF Team on 21 Dec 2015

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As we head into a new year, it’s a good time to look back at the research that kept the attention of PRF readers over the past year. Using Google…

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Highlights From the 2015 Annual Meeting of the Society for Neuroscience: Part 3

New optogenetic devices under development are ultra-miniaturized and implantable

by Stephani Sutherland on 17 Dec 2015

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The following is Part 3 of a three-part series of selected presentations from the 2015 annual meeting of the Society for Neuroscience, held October 17-21, 2015, in Chicago, Illinois,…

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Highlights From the 2015 Annual Meeting of the Society for Neuroscience: Part 2

Nerve growth factor antibody treatment quells pain in rodent models

by Stephani Sutherland on 14 Dec 2015

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The following is Part 2 of a three-part series of selected presentations from the 2015 annual meeting of the Society for Neuroscience, held October 17-21, 2015, in Chicago, Illinois,…

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Highlights From the 2015 Annual Meeting of the Society for Neuroscience: Part 1

Researchers explore cannabinoid strategies to quell pain

by Stephani Sutherland on 14 Dec 2015

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The following is Part 1 of a three-part series of selected talks from the 2015 annual meeting of the Society for Neuroscience, held October 17-21, 2015, in Chicago, Illinois,…

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Epigenetic Regulator Controls Development and Maintenance of Chronic Pain

Histone methyltransferase G9a reprograms potassium channel gene expression, drives pain following nerve injury in rodents

by Matthew Soleiman on 30 Nov 2015

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Chronic pain is associated with changes in expression of thousands of genes, making it hard to identify viable genetic targets for pain therapies. Pain researchers have thus turned to…

Research

Spinal Inhibitory Interneuron Populations Identified as Gatekeepers of Pain and Itch

Neurons containing parvalbumin or neuropeptide Y control mechanical allodynia and itch, respectively

by Allison Marin on 23 Nov 2015

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Two new mouse studies pinpoint two different groups of dorsal horn inhibitory interneurons as gatekeepers of mechanical allodynia and itch. In the first study, researchers led by Reza Sharif-Naeini,…

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A New Marker for A-beta Fibers Offers Appealing Target for Chronic Pain Treatment

Toll-like receptor 5 provides entryway for drugs to quell pain in several mouse models

by Stephani Sutherland on 16 Nov 2015

Among the hallmarks of neuropathic pain is the phenomenon of mechanical allodynia, in which normally non-painful stimuli—such as clothing rubbing against the skin, or even a person simply walking—produce…

Research

The Origins of Migraine: Inside or Outside the Brain?

Neuropeptide PACAP-38 triggers sensitization of central trigeminovascular neurons in rats, but both peripheral and central mechanisms likely contribute to the condition

by Matthew Soleiman on 4 Nov 2015

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Migraine is one of the most common and disabling chronic conditions throughout the world. The disorder is characterized by recurrent episodes of throbbing headache, often accompanied by nausea, vomiting,…

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Persistent Mechanical Pain: Delving Into Dorsal Horn Circuitry

Transient population of VGLUT3 neurons contributes to mechanical allodynia in mice

by Allison Marin on 14 Oct 2015

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New research has uncovered a spinal cord circuit, centered on excitatory interneurons in the deep dorsal horn, that plays a key role in persistent mechanical pain. The cells transiently…

Research

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…

Drug Development

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Sensory Afferents Share Information With Diverse Array of Neurons

Study complicates picture of intraganglion, intraspinal, supraspinal communications

by Stephani Sutherland on 30 Sep 2015

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Pain signals enter the spinal cord via primary sensory afferent neurons, which pass information along to ascending projection neurons that extend to the brain. But pain signals undergo processing…

Research

Extracellular Matrix Component of Joints Reduces Nociceptor Responses and Pain Sensitivity

Hyaluronan restrains opening of TRPV1 ion channel

by Matthew Soleiman on 23 Sep 2015

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Joints contain extracellular fluid that buffers the mechanical force imparted to joint tissues by bodily movement. Degradation of the polysaccharide hyaluronan (HA), a key component of the joint synovial…

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Prelimbic Circuitry Links Chronic Pain and Anxiety

Deactivation of a specific prefrontal neuron population via kinase signaling underlies the connection

by Matthew Soleiman on 25 Aug 2015

Comment

Chronic pain and anxiety are closely interconnected, with each increasing the likelihood of the other. Research published earlier this year pointed to synaptic plasticity in the anterior cingulate cortex…

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University of Texas System Hosts Pain Conference, Announces Formation of Texas Pain Research Consortium

Meeting draws pain researchers from across the state

by Dayna Loyd Averitt on 17 Aug 2015

This report was co-authored by Shivani Ruparel, University of Texas Health Science Center, San Antonio.

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Stem Cells Quell Neuropathic Pain in Mice

Single intrathecal injection of bone marrow stromal cells provides rapid and long-lasting relief from mechanical and thermal pain

Allison Marin on 11 Aug 2015

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Preclinical evidence that bone marrow stromal cells (BMSCs) are a promising treatment for neuropathic and inflammatory pain continues to accumulate. A new study led by Ru-Rong Ji and Gang…

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Highlights From the 10th Annual NIH Pain Consortium Symposium

Mitchell Max Award finalists present findings on contributions of exercise and stress to pain, and social disparities in pain care

by Stephani Sutherland on 7 Aug 2015

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No institute at the National Institutes of Health (NIH) is dedicated exclusively to pain research, so the multi-institute Pain Consortium was created in 1996 to coordinate research across the…

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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…

Drug Development

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Sex Differences in Immune Cell Mediation of Pain

Microglia crucial for mechanical pain hypersensitivity in male mice, T lymphocytes vital in females

by Allison Marin on 21 Jul 2015

Comment

A substantial body of evidence points to microglia as critical contributors to pain signaling. However, new findings suggest that, unlike in male mice, microglia are not necessary for mechanical…

Research

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

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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

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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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Highlights From the 2015 Annual Scientific Meeting of the American Pain Society: Part 1

Mining the sleep-pain connection for new therapeutic strategies

by Stephani Sutherland on 26 Jun 2015

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The following is Part 1 of a three-part series of selected talks from the 34th Annual Scientific Meeting of the American Pain Society (APS) held May 13-16, 2015, in…

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Highlights From the 2015 Annual Scientific Meeting of the American Pain Society: Part 2

Keratinocytes emerge as active players in sensing pain

by Stephani Sutherland on 26 Jun 2015

The following is Part 2 of a three-part series of selected talks from the 34th Annual Scientific Meeting of the American Pain Society (APS) held May 13-16, 2015, in…

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Highlights From the 2015 Annual Scientific Meeting of the American Pain Society: Part 3

Sensory neuron, immune cell signaling turn acute pain chronic

by Stephani Sutherland on 26 Jun 2015

The following is Part 3 of a three-part series of selected talks from the 34th Annual Scientific Meeting of the American Pain Society (APS) held May 13-16, 2015, in…

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PRF Announces Partnership With the Rita Allen Foundation

Two-year grant will support development of lay materials to help raise public awareness of chronic pain and rally support for research

by PRF Team on 15 Jun 2015

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PRF is pleased to announce that the Rita Allen Foundation will support “Coverage of Pain Research for Patients to Elevate Public Awareness and Understanding of Chronic Pain,” a new…

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Newly Identified Mutations Cause Pain Insensitivity

Gene with epigenetic control of sensory neuron development required for pain perception

by Stephani Sutherland on 11 Jun 2015

People with congenital insensitivity to pain (CIP) cannot sense painful stimuli, and as a result continually suffer painless yet detrimental tissue damage, sometimes resulting in death. Mutations in a…

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