No Pain Relief Found With Paracetamol (acetaminophen) for Acute Back Pain

PainRelief.com Interview with:
Christina Abdel Shaheed PhD
Researcher and Academic
University of Sydney

Dr. Abdel Shaheed

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

Response: Paracetamol (acetaminophen) is one of the most widely used drugs for pain relief globally. Our study (https://onlinelibrary.wiley.com/doi/full/10.5694/mja2.50992) examined the evidence on the efficacy of paracetamol versus placebo for 44 different pain conditions. There is strong evidence paracetamol provides greater pain relief than placebo for four conditions: craniotomy, knee or hip osteoarthritis, tension headache and perineal pain following childbirth, however sometimes the effects were very small.

Paracetamol was no more effective than placebo for acute low back pain. There is uncertainty regarding the benefits of paracetamol for the remaining 39 pain conditions. To note, most studies evaluated single doses of the pain reliever, which does not reflect typical use of the medicine.


PainRelief.com: What should readers take away from your report?

Response: If people are considering paracetamol for their pain, the recommendation is to:

  • Stick within the safe limits for using paracetamol (maximum 4 g daily for adults, which will vary depending on the formulation used).
  • Bear in mind there are different types of paracetamol products (long-acting, which should be taken less frequently, versus short-acting); and cold and flu preparations (including decongestant) and popular over-the-counter products for pain relief (including ibuprofen) can also contain paracetamol.
  • Do not use paracetamol for more than a few days at a time unless specifically advised to by a doctor or pharmacist.
  • Consider combining the medicine with other non-drug strategies to optimise pain relief, particularly for conditions like osteoarthritis e.g. exercise and healthy eating.

PainRelief.com: What recommendations do you have for future research as a result of this work?

Response: High quality clinical trials evaluating typical use of paracetamol are needed to resolve the uncertainty around its effectiveness for the majority of pain conditions.

Disclosures: Some of the authors on this study were also involved in the PACE trial which evaluated the efficacy of paracetamol vs placebo for acute low back pain.

Citation:

Abdel Shaheed, C., Ferreira, G.E., Dmitritchenko, A., McLachlan, A.J., Day, R.O., Saragiotto, B., Lin, C., Langendyk, V., Stanaway, F., Latimer, J., Kamper, S., McLachlan, H., Ahedi, H. and Maher, C.G. (2021), The efficacy and safety of paracetamol for pain relief: an overview of systematic reviews. Med J Aust, 214: 324-331. https://doi.org/10.5694/mja2.50992

The information on PainRelief.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

Study Evaluates Placebo Effect of CBD on Pain Relief

PainRelief.com Interview with:
Martin De Vita, CPT, MS, USA
Doctoral Candidate
Clinical Psychology Department
Syracuse University

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

Response: Seemingly out of nowhere, cannabidiol (CBD) products became immensely popular. Cross-sectional studies showed widespread use among the public for various clinical conditions. Pain was by far the most commonly reason cited for using CBD. However, no human experimental pain studies had been conducted to evaluate the analgesic effects of CBD. A lot of people questioned whether CBD effects on pain were just a placebo.

To answer this question, we tested people’s baseline pain responding using sophisticated equipment capable of delivering safe, but painful stimulation that activates and evaluates human nervous system processes. Then we administered either CBD or a placebo and re-tested these pain outcomes to see how they changed. We took it a step further and manipulated the information that participants were given about which substance they received. So in some conditions, participants were told they got CBD, even though it was just a placebo. In other conditions, participants were told they got an inactive substance, despite actually receiving CBD. This way, we could test whether simply telling someone that they had received CBD would have an effect on their pain. These are called expectancy effects and there is a large body of literature that supports this phenomenon.

When we looked at the data, we found that CBD analgesia was actually driven by both expectancies (placebo analgesia) and pharmacological action. We also found that these manipulations affected different pain outcomes. We found that both CBD and expectancies reduced pain unpleasantness but not pain intensity. The results were complex in that CBD and expectancies for receiving CBD differentially affected various outcomes. This was exciting because we are left with even more questions to investigate in future research.

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Tapentadol Provided Pain Relief and Improved Sleep in Patients with Chronic Musculoskeletal Pain

PainRelief.com Interview with:
Dr Renato Vellucci
Contract Professor University of Florence
Pain and Palliative care Clinic
University Hospital of Careggi
Florence, Italy

Dr. Vellucci

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

Response: Chronic low back pain (CLBP) is the most prevalent chronic pain (CP) condition and the leading global cause of years lived with disability. According to the axiom pain as a biopsychosocial issue, mood and sleep disturbances represent key issues. However, the impact of different analgesic therapies on quality of life (QoL) and functional recovery has been poorly assessed to date. Focusing on combination of chronic pain and sleep, they both perform a mutual reinforcement.

Pain disorganizes the sleep architecture, and disturbed and unrefreshed sleep increases spontaneous pain and lowers pain thresholds. Sleep disorders may augment stress levels, thus making it difficult for patients to perform simple tasks impairing their cognitive ability. Poor sleep may predict the growth and intensification of pain over time, with increased insomnia symptoms being both a predictor and an indicator of worse pain outcomes and physical functioning status over time. Epidemiology of chronic pain unequivocally demonstrates the role of sleep quality in the development of chronic pain.

Notwithstanding this strong two-way relationship between chronic pain and sleep, little knowledge is available about the neurochemical determinants of this interplay and therapeutical strategies to break this vicious circle. Fifty percent of people with chronic low back pain have sleeping disturbances, with an 18-fold increase in insomnia versus healthy people. A recent study investigated the relationship between sleep disturbances and back pain and found that it is two sided with sleep disturbance being associated with risk of back pain whilst back pain can also lead to sleep disturbances. Thus, it can be hypothesized that, by reducing pain and physical dysfunction, sleep quality could be improved, thus enriching the QoL of people with CLBP.

Similarly, improvements in sleep after cognitive behavioral therapy in patients with chronic pain due to osteoarthritis were associated with reduced pain. Earlier evidence suggested that tapentadol prolonged-release treatment ameliorate in parallel QoL and sleep quality in a greater proportion of patients compared to that of patients following oxycodone/naloxone prolonged- release treatment (50% versus 37.7%). Other tapentadol studies conducted in a real-life context documented, along with effective pain control, similar improvements in mental and physical health and suggested beneficial effects in terms of less night awakenings and greater percentages of patients reporting restful sleep.

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Costs of Compounded Pain Relief Medications Vary Widely Among Local Pharmacies

PainRelief.com Interview with:
Youssef Labib
PharmD Candidate
University of Waterloo School of Pharmacy

Youssef-Labib
Youssef Labib

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

Response: Compounded pain medication price data was gathered from over 30 community pharmacies for the sole purpose of directing our patients to both the most accessible and affordable compounding pharmacy.

A drastic variation in price was noticed and this report was published to comment on potential implications.

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New Class of Drugs May Provide Pain Relief Without Need for Opioids

PainRelief.com Interview with:
John Traynor, PhD
Edward F Domino Research Professor
Professor and Associate Chair for Research
Department of Pharmacology, Medical School
Professor of Medicinal Chemistry, College of Pharmacy
University of Michigan, Ann Arbor MI

Dr. Traynor

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

Response: Response: Morphine and related drugs acting at the mu-opioid receptor are the most effective treatment for moderate to severe pain, yet their use is limited by serious on-target side effects including respiratory depression, and physical and psychological dependence that has led to the opioid crisis.  Current opioid drugs are required because our own endogenous pain relieving chemicals, the enkephalins and endorphins opioid peptides, cannot efficiently relieve pain.  

We have discovered a class of drugs (positive allosteric modulators, PAMs) that bind to the mu-opioid receptor to enhance the activity of endogenous opioids.  These “enkephalin amplifiers” afford pain relief in mouse models without the need for morphine-like compounds and do so with a much reduced side-effect profile.

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Chronic Low Back Pain: Spinal Manipulation Therapy May Reduce Opioid-Related Adverse Effects

PainRelief.com Interview with:
Jim Whedon DC, MS
Director of Health Services Research
SCU Health System
Southern California University of Health Sciences
Whittier, CA

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

Response:    Current evidence-based guidelines for clinical management of chronic low back pain (cLBP) include both pharmacological and non-pharmacological approaches.

Both Opioid Analgesic Therapy (OAT and Spinal Manipulative Therapy (SMT) are effective treatments for cLBP and are provided under Medicare for older adults with cLBP, but the long-term safety of OAT is uncertain, and the dangers of opioid misuse are well known. Older adults are at particularly high risk of adverse drug events (ADEs),but they nevertheless receive more opioid analgesics than any other age group. SMT is established as an effective non-pharmacologic treatment for cLBP, but little is known about the safety of long-term treatment with SMT. The objective of our study was to compare SMT and OAT to determine the impact of SMT on the risk of ADEs among older adults receiving long-term care for cLBP.

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Targeted Smartphone Exercise Program Can Provide Pain Relief from Knee Arthritis

PainRelief.com Interview with:
Ana M Valdes MA PhD
Professor in Molecular and Genetic Epidemiology
NIHR Nottingham Biomedical Research Centre – Research Area Lead
Associate Editor European Journal of Clinical Nutrition
School of Medicine
University of Nottingham

Dr. Valdes

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

Response: Knee osteoarthritis and knee pain affect a large proportion of middle age and aging individuals and this are  an increasing problem. Physical exercises aimed at strengthening and stabilising the muscles in the legs and hips  are known to be highly effective in reducing pain and improving the ability to walk and get on with life. But a key challenge is how to deliver such gradual exercises in a way that does not require people to travel to see a physiotherapist or a doctor, particularly given the issues raised by  lockdown both in terms of the Covid-secure challenges face to face visits and also given the strain that the pandemic has put on health services.  

Our  study was the first randomised controlled trial in the UK where we were had people with painful knee osteoarthritis either do only what their doctors normally recommend or, in addition, follow a programme of exercised developed in Sweden delivered via  smartphone app. The research participants were assessed for knee inflammation, knee pain, pain sensitivity around the knee, muscle strength, and ability to walk and get up from a chair both before and after the 6 week smartphone delivered intervention (or a 6 week period simply following any advice they had from their family doctor).

Transcranial Neuromodulation Studied for Pain Relief

PainRelief.com Interview with:
Markus Ploner MD
Professor of Human Pain Research
Department of Neurology
Technische Universität München
Munich, Germany

Prof. Ploner

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

Response: Recent studies in humans and animals have revealed that pain is associated with rhythmic brain activity termed neural oscillations. In particular, changes of neural oscillations at alpha (8 – 13 Hz) and gamma (30 – 100 Hz) frequencies in somatosensory and prefrontal brain areas have been related to pain. Thus, modulating neural oscillations to eventually modulate pain is a promising novel approach for pain treatment.

Transcranial alternating current stimulation (tACS) is an emerging neuromodulation technique which aims at non-invasively modulating neural oscillations in the human brain. During tACS, a weak alternating current is applied to the scalp with the goal of entraining neural oscillations at the stimulation frequency, thereby increasing their amplitude. The appeal of tACS is that it is non-invasive, safe, cost-efficient, and potentially mobile which allows for broad clinical applications. Thus, tACS is increasingly explored as a new treatment approach for neuropsychiatric disorders.

In our study, we therefore explored the potential of tACS to modulate pain. We systematically applied tACS at alpha and gamma frequencies or sham tACS over somatosensory and prefrontal cortices during tonic experimental pain in healthy human participants.

PainRelief.com: What are the main findings?

Response: Our main findings are that, using the current setup, tACS did not modulate the perception of pain. Bayesian statistics further supported a lack of tACS effects in most conditions including prefrontal and gamma tACS. The only exception was tACS at alpha frequencies over somatosensory cortex where evidence for tACS effects on pain perception was inconclusive. 

PainRelief.com: What should readers take away from your report?

Response: Readers might take away three key points.

First, neurophysiological studies indicate that modulating neuronal oscillations to eventually modulate pain is a promising novel approach for the treatment of pain.

Second, tACS is one non-invasive and simple approach to modulate neuronal oscillations.

Third, our mostly negative findings show that we are not there yet.    

PainRelief.com: What recommendations do you have for future research as a result of this work?

Response: A very general recommendation is that rigorous, well-controlled and transparent studies are needed to further explore the potential of tACS (and other neuromodulatory techniques) for treating pain. Furthermore, we should ideally make all our data available to the public so that the whole research community can take advantage of them. Finally, to advance the field, we should not only publish positive but also negative findings, as done here. 

A more specific recommendation is that modulating neuronal oscillations at alpha frequencies over somatosensory brain areas is the most promising approach for further tACS studies.

Citation:

May ES, Hohn VD, Nickel MM, Tiemann L, Gil Ávila C, Heitmann H, Sauseng P, Ploner M. Modulating Brain Rhythms of Pain using Transcranial Alternating Current Stimulation (tACS) – A Sham-controlled Study in Healthy Human Participants. J Pain. 2021 Apr 9:S1526-5900(21)00191-7. doi: 10.1016/j.jpain.2021.03.150. Epub ahead of print. PMID: 33845173.

The information on PainRelief.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

Redheads May Experience Pain Differently

PainRelief.com Interview with:
David E. Fisher MD, PhD
Edward Wigglesworth Professor & Chairman
Dept of Dermatology
Director, Melanoma Program MGH Cancer Center
Director, Cutaneous Biology Research Center
Massachusetts General Hospital
Harvard Medical School

Dr. Fisher

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

Response: This study followed up on prior published work from other investigators which demonstrated altered pain thresholds in humans and mice who had the redhair light-skin phenotypes.  The key focus of our current study was to firstly validate the overall findings, and then to  the mechanistic basis for the differences.  Of note, our laboratory does not primarily focus on the science of pain or nociceptive, but rather on skin and melanoma. For this reason we had accumulated a number of valuable genetic models of pigmentation (such as redhaired mice harboring alterations in the identical gene implicated in human red hair).  These mouse models served as the key resources for carrying out the current study.

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Migraine: Galcanezumab (Emgality®) for Pain Relief in Patients with Previous Preventive Medication Failures

PainRelief.com Interview with:
Dulanji K. Kuruppu, MD

Medical Advisor, Migraine & Headache Disorders
US Medical Affairs
Eli Lilly and Company
LTC-South, Indianapolis IN 46221 U.S.A.

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

Response: Galcanezumab is a monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) and is approved for the preventive treatment of migraine and for the treatment of episodic cluster headache in adults. The CONQUER study assessed the efficacy and safety of galcanezumab in 462 adults with episodic or chronic migraine who previously did not benefit from 2 to 4 standard-of-care migraine preventive medication categories. This study consisted of a 3-month double-blind, placebo-controlled period (months 1-3) followed by an open-label period (months 4-6). The primary endpoint, which was the mean change from baseline in the number of monthly migraine headache days for galcanezumab vs placebo over months 1-3, was met. In this post-hoc analysis, we assessed onset of effect of galcanezumab in the CONQUER population.

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