NYU Lab Harnesses Gene Therapy to Tackle Chronic Pain

PainRelief.com Interview with:
Rajesh Khanna, PhD

Director, NYU Pain Research Center
Professor, Department of Molecular Pathobiology
Professor, Department of Neuroscience and Physiology
Investigator, Neuroscience Institute
New York University


PainRelief.com: What is the background for this study?

Response: Chronic pain affects an estimated 20-30% of the global population, significantly impacting quality of life and mental health. It poses substantial socioeconomic burdens, with costs relating to healthcare and lost productivity. Despite its prevalence, chronic pain remains underdiagnosed and undertreated worldwide, highlighting a crucial need for enhanced awareness, research, and therapeutic strategies.

Among the many targets being pursued for the development of drugs against chronic pain conditions are key proteins in neurons that are involved in the signaling of pain. A key family of these targets is the voltage-gated sodium channel family. Among them, the Nav1.7 sodium channel plays a critical role in the development and maintenance of chronic pain. It is an integral part of the peripheral nervous system and is highly expressed in nociceptive (pain-sensing) neurons, including the dorsal root ganglia and sympathetic ganglion neurons.

Nav1.7 channels act as a threshold channel, amplifying small sub-threshold depolarizations and generating action potentials, which are the electrical signals responsible for transmitting sensory information, including pain, to the brain. In essence, they work as a key amplifier of signals from peripheral pain-sensing neurons to central pain pathways.

Certain genetic mutations that cause either a gain or loss of Nav1.7 function can lead to conditions associated with altered pain perception. Gain-of-function mutations, which increase the activity of the channel, can lead to pain syndromes like Inherited Erythromelalgia (IE) and Paroxysmal Extreme Pain Disorder (PEPD). In contrast, loss-of-function mutations, which decrease or eliminate the activity of Nav1.7, result in Congenital Insensitivity to Pain (CIP), a condition where individuals are unable to feel pain.

Given this integral role, Nav1.7 has become a focus of interest as a target for new analgesic drugs. The development of Nav1.7 inhibitors could offer a new avenue for more effective and targeted treatment strategies for chronic pain conditions. It’s a promising area of research, though there are still challenges to be met, such as achieving sufficient specificity for the Nav1.7 channel to avoid side effects associated with other sodium channels.

In the NYU Pain Research Center in the College of Dentistry at New York University (https://dental.nyu.edu/research/pain-research-center.html), the Khanna lab is pursuing alternative ways to target Nav1.7 for pain relief.

Continue reading

State-Level Policies May Reduce Disparities in Pain Prevalence

PainRelief.com Interview with:
Rui Huang MA

Department of Sociology
University at Buffalo
Buffalo, NY

PainRelief.com: What is the background for this study?

Response: In the U.S., approximately 58.5 million people (23.7% of adults) have arthritis, and at least 15 million of them suffer from severe arthritis-attributable joint pain. Severe joint pain is strongly associated with impaired functioning, disability, mortality, and limited life chances. People with less education disproportionately suffer from joint pain and reduced quality of life.

However, existing research on social determinants of pain relies primarily on individual-level data; it rarely examines the role of macro sociopolitical contexts, such as state-level policies.  Moreover, relatively little is known about the geographic distribution of pain, and even less is known about geographic variation in socioeconomic disparities in pain. 

To our knowledge, this is the first study to look at how U.S. state-level policies and characteristics shape risk of pain, and educational disparities in pain.

Continue reading

Study Demonstrates Feasibility of Engineering Biomechanical Scaffolds for Cartilage Repair

PainRelief.com Interview with:
Prof. Hongbin Li
Department of Chemistry
The University of British Columbia,
Vancouver, British Columbia, Canada

PainRelief.com: What is the background for this study?

Response: Cartilage degeneration and damage are significant health issues, and cartilage repair is a major challenge because cartilage has a limited capacity for self-repair. One of the strategies for cartilage regeneration is to use scaffolds to promote the growth and differentiation of chondrocytes. For this, the scaffolds need to be tough and stiff to meet the requirements of cartilage regeneration. However, it is challenging to engineer highly stiff and tough materials, as stiffness and toughness are often self-conflicting to each other. In this work, we developed a novel strategy to engineer stiff yet tough protein hydrogels whose mechanical properties mimic those of cartilage. Such engineered stiff and tough protein hydrogels were tested as implants to repair osteochondral defect in an animal model.

Study Finds Opioids No Better Than Placebo for Back or Neck Pain Relief

PainRelief.com Interview with:
Christine Lin | Professor
The University of Sydney                                           
Sydney Musculoskeletal Heatlh
Faculty of Medicine and Health, Sydney School of Public Health
Institute for Musculoskeletal Health                             
Gadigal Country King George V Building
Royal Prince Alfred Hospital NSW Australia

PainRelief.com: What is the background for this study?

Response: Opioids are one of the most commonly prescribed pain medicines for low back pain and neck pain, but before this trial we did not have robust, direct evidence that they are effective for acute low back pain and neck pain.

PainRelief.com: What are the main findings?

Response: We found that taking opioids did not relieve acute low back pain and neck pain in the short term, and led to worse outcomes in the long term. We randomly assigned people with acute low back pain or neck pain to take opioids or placebo (identical tablets but with no active ingredients) for up to 6 weeks, in addition to getting the best advise on how to manage their pain from their doctor. We followed these people up for 1 year.

At 6 weeks, people in the opioid group did not report lower pain levels compared to people in the placebo group. Nor were there differences in pain outcomes at 2 and 4 weeks, or in other outcomes such as physical function, recovery time, or quality of life.

Surprisingly at 1 year, people who took opioids had slightly worse pain and an increased risk of opioid misuse.

Racial Differences in Chronic Pain Among Football Players

PainRelief.com Interview with:
Robert R Edwards, Ph.D.
Associate Professor of Anaesthesia
Pain Management Center
Brigham and Women’s Hospital

PainRelief.com: What is the background for this study?

Response: Chronic pain affects over 100 million American adults, and is a leading cause of reduced quality of life. However, in the US, the of burden of pain falls most heavily on members of racial and ethnic minority groups who frequently report more pervasive and severe pain compared with those in the majority.

In this study we evaluated race differences in pain among nearly 4,000 former professional American-style football players who self-identified as either Black or white.

Continue reading

Leisure Time Exercise May Increase Pain Tolerance

PainRelief.com Interview with:
Anders Pedersen Årnes
Department of Pain
University Hospital of North Norway in Tromsø

PainRelief.com: What is the background for this study?

exercise-pain-elderly

Response: The international association for the study of pain has actually deemed 2023 the global year for integrative pain care, which emphasizes non-drug, self-management care.

Exercise is an important way of managing chronic pain conditions, as there are few real pharmaceutical alternatives for treating them. Several studies point towards our ability to process pain signals as a possible contributing reason to chronic pain, as that often is seen to behave differently in those with chronic pain to those without. Since physical activity also appears to be a useful tool for preventing and treating chronic pain, we are trying to figure out whether this effect on pain sensitivity tolerance be one of the mechanisms through which physical activity protects against chronic pain.

This current study represents a first epidemiological look at how physical activity over time relates to pain tolerance over time in a whole population.

Study Finds More Than 10 Million New Cases of Adult Chronic Pain Per Year

PainRelief.com Interview with:
Richard L. Nahin, MPH, PhD

National Center for Complementary and Integrative Health
National Institutes of Health, Bethesda, Maryland

PainRelief.com: What is the background for this study?

Response: While there has been extensive research examining the prevalence of chronic pain, far less is known about the incidence of chronic pain.  Understanding the incidence of chronic pain is critical to understanding how such pain manifests and evolves over time.

Continue reading

Key Driver of Neuropathic Pain Identified by Baylor College of Medicine Scientists

PainRelief.com Interview with:
Kimberley Tolias, Ph.D.
Professor
Department of Neuroscience
Biochemistry & Molecular Biology
Baylor College of Medicine
Houston, TX 77030

PainRelief.com: What is the background for this study?

Response: Neuropathic pain is a chronic pain condition that affects millions of people worldwide, significantly impairing their quality of life.  Symptoms of neuropathic pain include spontaneous shooting or burning pain, pain from activities that don’t normally cause pain (allodynia), and heightened pain sensitivity (hyperalgesia).  Current treatment options for neuropathic pain, such as opioids, focus on symptom suppression and are generally ineffective and often cause unwanted side effect.  In order to develop safer, more effective chronic pain treatments, we need to better understand the processes that lead to neuropathic pain.

Neuropathic pain is caused by nerve damage from a variety of insults (e.g., injury, disease, infection, chemotherapy drugs), which trigger structural and functional changes in the neurons and synaptic connections that transmit pain signals.  These activity-dependent alterations in somatosensory neural circuits are thought to be responsible for the persistent symptoms associated with chronic pain, but how they are induced and maintained following nerve injury or disease remains unclear.  To address this problem, our research team, including lead and co-corresponding author Dr. Lingyong Li (now at University of Alabama at Birmingham), investigated the mechanisms that underlie neuropathic pain, with the goal of identifying strategies to prevent or control it.

Continue reading

COCHRANE: Poor Evidence for Prescription Antidepressants for Pain Relief

PainRelief.com Interview with:
Professor Tamar Pincus PhD
Professor in Health Psychology
Dean of the Faculty of the Environment and Life Sciences
University of Southampton

PainRelief.com: What is the background for this study?

Response: Antidepressants are recommended by guidelines for many chronic pain conditions. The most common prescribed antidepressant in amitriptyline. We carried out the largest and most systematic review of all antidepressants for all pain condition, at any dose, to test whether they were effective at reducing pain, increasing physical function, and improving mood and sleep. We reviewed 176 trials with almost 30,000 participants. We rated each study for its methodology so we could rank each drug according to how much we could be certain of the evidence.

Cognitive Functional Therapy: Clinical and Cost-Effective Pain Reduction For Chronic, Disabling Low Back Pain

PainRelief.com Interview with:
Peter Kent
Adjunct Associate Professor
Curtin School of Allied Health
Curtin University, Perth
WA, Australia

PainRelief.com: What is the background for this study?

Response: Although there had been clinical trials of Cognitive Functional Therapy (CFT) with promising results, there had not been a fully powered trial comparing CFT with usual care, nor any trials in Australia. Previous trials had included a maximum of 3 CFT clinicians, whereas the RESTORE trial included the training of 18 physiotherapists to CFT competency who had minimal prior exposure to CFT. No previous CFT trial had included an evaluation of 6161615g8cost effectiveness of CFT, nor examined whether the use of wearable motion sensor biofeedback might enhance the effect of CFT.

Continue reading