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A Must listener – Stephen McMahon at PRF

Musings on the Progress of Pain Research: A Podcast with Stephen McMahon


You could spend 45 minutes in a whole bunch of worse ways…
“McMahon discusses his early days in the pain research field, what it was like to train with Patrick Wall, the gate control theory of pain, central sensitization, and much more”

“Not the smartness of people but the smartness of nature, I still think that there are many thinks to be discovered from the natural world that would greatly help in our efforts to develop analgesics”


Stephen McMahon


Go to Podcast here

About Stephen McMahon

In this third IASP podcast features pioneering pain researcher Stephen McMahon, PhD. Dr. McMahon is Sherrington Professor of Physiology at King’s College London, UK, where he leads a research group in clinical neuroscience. He also directs the Wellcome Trust Pain Consortium, an international network of leading pain researchers. He trained under Patrick Wall at University College London before moving to King’s College London in 1985 to run his own lab. His major research interest is pain mechanisms, and he has been working to identify and understand pain mediators. More recently, he has focused on neuroimmune interactions and the role of genetics and epigenetics in pain.

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Meet Dr. Kirsty Bannister

Kirsty Bannister


I lead the Bannister lab group, where we focus on the biological, pharmacological and anatomical basis of pain pathways and their plasticity in chronic pain states. Chronic pain affects up to 20% of the adult population and can occur in the presence or absence of any past injury or evidence of body damage. Modules that I teach on include Physiology and Pharmacology of the Central Nervous System, Pharmacology of Neurological and Psychiatric Disorders, Core Year One Fundamentals of Pharmacology, and Neuroscience. My lab’s research is funded by the Academy of Medical Sciences and the NC3Rs.

Please see my Research Staff Profile for more detail

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Central Nervous System Targets: Supraspinal Mechanisms of Analgesia

Central Nervous System Targets: Supraspinal Mechanisms of Analgesia

In the run up to Dr Kirsty Bannister’s Home Brew we will be sharing her work with you!

Pain care needs to understand and be able to integrate current discoveries in lab-based science.

Check out this article and drop your thoughts in the comments!
“Central Nervous System Targets: Supraspinal Mechanisms of Analgesia”

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Discovering novel & effective pain treatments

About the event

We are SO excited to welcome Dr. Kirsty Bannister to Le Pub

Kirsty will be talking about the reality of discovering novel and effective pain-relieving treatments through performing bench to beside translational research.

Chronic pain affects up to 20% of the adult population and can occur in the presence or absence of any past injury or evidence of body damage. ‘Nothing is more unique than our experience of pain and the idea that the same stimulus could evoke a different pain sensation in different individuals has always fascinated me’.

‘There have been great improvements in our understanding of pain physiology and pathophysiology over the years, but why hasn’t this translated to a met clinical analgesic need? By discussing the ways in which we currently assess nociception and pain in non-human and human experimental models, we will slowly unravel the intricacies and challenges of treating persistent pain in varied patient groups’.

This is going to be an incredible Le Pub Homebrew!

World Event Times

London, Thursday, 18 March 2021, 20:00 GMT

Amsterdam, Thursday, 18 March 2021, 21:00 CET

New York, Thursday, 18 March 2021, 16:00 EDT

Dr. Kirsty Bannister

Kirsty Bannister is a Lecturer in the Institute of Psychiatry, Psychology and Neuroscience at Guy’s campus, King’s College London. Kirsty does research in neuropharmacology.

Kirsty leads the Bannister lab group, where she focuses on the biological, pharmacological and anatomical basis of pain pathways and their plasticity in chronic pain states. Modules that she teaches on include Physiology and Pharmacology of the Central Nervous System, Pharmacology of Neurological and Psychiatric Disorders, Core Year One Fundamentals of Pharmacology, and Neuroscience.

Cancellation Terms

Places can be cancelled and refunded up to 48 hours before the start of the event. Within 48 hours of start time no refund.


Please note that Le Pub Home Brew is a LIVE EVENT. We are looking at options for giving access to recordings in the future, but right now, we are doing what we are best at – bringing you awesome live and interactive learning events!

Kirsty Bannister Efic interview with Morten Hoegh

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Find out when exercise will help or hinder when you’re experiencing pain

Find out when exercise will help or hinder when you're experiencing pain

About this event

Exercise is a recommended treatment for those with chronic pain. However, individuals with chronic pain have significant pain during activity that can interfere with exercise treatments. We will discuss the underlying neurobiology for how physical activity increases and decreases pain, the clinical implications of these findings, and how treatment with TENS can reduce movement-evoked pain.

World Event Times

London, Thursday, 18 February 2021, 20:00:00 GMT

Amsterdam, Thursday, 18 February 2021, 21:00:00 CET

New York, Thursday, 18 February 2021, 15:00:00 EST

Kathleen A. Sluka, PT, PhD, FAPTA

Professor of Physical Therapy and Rehabilitation Science

Dr. Sluka’s laboratory studies the peripheral and central mechanisms of chronic musculoskeletal pain, and non-pharmacological treatment for chronic pain. These studies involve the use of animal models of muscle pain developed and characterized in Dr. Sluka’s laboratory, as well as projects in human subjects. We use a variety of techniques to address these questions including cell culture, molecular biology, genetic manipulations, behavioral pharmacology, and standard clinical trial methodology. Our overall goals are to improve the management of pain for people with a variety of musculoskeletal pain conditions by discovering the underlying mechanisms that lead to the development of chronic pain, discovering new therapies for pain management, and improving the use of currently available treatment for pain.

Cancellation Terms

Places can be cancelled and refunded up to 48 hours before the start of the event. Within 48 hours of start time no refund.


Please note that Le Pub Home Brew is a LIVE EVENT. We are looking at options for giving access to recordings in the future, but right now, we are doing what we are best at – bringing you awesome live and interactive learning events!

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Pain, hyperalgesia and activity in nociceptive C units in humans

Pain, hyperalgesia and activity in nociceptive C units in humans


Check out this great bit of work by LaMotte et al from 1992.
Here’s some simple reflections of the science:
– First they’re exploring activity of nociceptors in humans. That means someone volunteered for this!
– They use a crude way of ‘finding’ C-mechanoheat nociceptive units (CMHs) – scrape the skin or pinch it between the fingers
– It is only classified as a C-fibre if the conduction velocity is less than 2 m/s
– It is only classified as mechanoheat nociceptor if it selectively responds to technical or heat stimuli which typically cause pain
– They carefully map the receptive field
– Then they inject capsaicin i.e. the active component of chili peppers
– Interestingly, they tried to limit the numerical rating scale of pain to sensation only (is it possible to separate yourself from the unpleasantness or tolerability?)
What did they find?
– Heat and pain threshold reduced after injecting capsaicin. Now temperatures as low as 30C were felt as painful!
– Cooling the skin reduced pain and the spontaneous firing of the CMHs
– Warming increased this again!
– There was evidence of mechanical hyperalgesia i.e. increased pain to mechanical stimuli
– Some of this was outside of the skin zone affected by the injection i.e. ‘secondary hyperalgesia’
– There was evidence of analgesia around the injection site too
A simple summary:
– Ask a bunch of crazy people if it’s ok to inject some chili into them
– Scrape, pinch, electrically stimulate, heat and cool them whilst asking if it hurts
– Find that the injection makes these things simultaneously hurt more or less depending on where you do it
– Then discover something totally cool but keep in under wraps
Here’s the cool discovery – hang in there!
“A few presumably chemosensitive C units were discovered serendipitously during studies of CMH units….” In other words, it looks like these researchers were (?) the first to discover sleeping or silent nociceptors in humans. BOOM
It’s worth hearing their summary and considering some of the current proposed models to understand pain with.
“An interesting question is why pain from intradermal injection of [capsaicin] is so intense….One possible explanation might be that the discharge pattern in C polymodal nociceptors on capsaicin injection is irregular, with bursts of impulses …. It is conceivable that such high instantaneous firing rates during bursts of impulses could give rise to considerable pain due to temporal summation….It is also possible that several types of nociceptors are activated by capsaicin. Candidate nociceptors in addition to the CMHs could include purely chemosensitive units as well as the heat nociceptors that respond both to noxious heat and to capsaicin but not to mechanical or cold stimuli.”

Research papers

You can access Lemotte’ paper here

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Central Sensitization: Viewpoints in JOSPT


This article is recently published in JOSPT – (here)


Central sensitization is a physiological mechanism associated with enhanced sensitivity and pain responses. At present, central sensitization cannot be determined directly in humans, but certain signs and symptoms may be suggestive of it. Although central sensitization has received increasing attention in the clinical literature, there is a risk that certain distinctions are being lost. This paper summarizes current knowledge of the physiology of central sensitization and its possible manifestations in patients, in order to inform a debate about the relevance of central sensitization for physical therapists. It poses 6 challenges associated with the application of central sensitization concepts in clinical practice and makes suggestions for assessment, treatment, and use of terminology. Physical therapists are asked to be mindful of central sensitization and consider potential top-down as well as bottom-up drivers, in the context of a person-centered bio- psychosocial approach.

Key Points

  • Central sensitization is a physiological and reversible mechanism associated with enhanced sensitivity and pain responses.
  • Until better markers are available, detection of central sensitization in humans remains tentative.
  • We must be careful that the concept of central sensitization is not used interchangeably with psychological manifestations.
  • Let us keep an open mind about central sensitization as our knowledge about this in

About the author

Matt Low

Matt is a Consultant Physiotherapist in the NHS and is a visiting associate at the Orthopaedic Research Institute at Bournemouth University. He qualified from the University of Southampton and is a member of the Musculoskeletal Association of Chartered Physiotherapists (MACP) following completion of his Masters degree in Neuromusculoskeletal Physiotherapy at the University of Brighton.

Matt has lectured and examined for pre-registration and post-registration students at a number of Universities in the South of England. He has lectured on subjects such as motor control, spinal manipulation and clinical reasoning skills. He has interests in compassionate person-centred care, the theory of causation within the healthcare setting, philosophy, reflective practice and critical thinking skills.


Matt will join us in the future for a f2f course. This particular article is a great pre-read for Melissa Farmer’ talk in Le Pub Home Brew

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Part 2 – Melissa Farmer on Central Sensitization

The Original Phenomenon, Play by Play

Under normal circumstances, a nociceptive signal reflects the features of a noxious stimulus. With central sensitization, nociception reflects altered excitability of a spinal cord circuit.

In this way, central sensitization marks the first point when nociception becomes independent of the environment.

Over 35 years ago, Clifford Woolf formally confirmed a hypothesis that had been floating around in the pain literature for many decades. Pain physiologists had long suspected that nociceptive signals could somehow be amplified in the spinal cord, but they didn’t have the technology to understand how this could happen. A major challenge was differentiating spinal-specific effects from peripheral nociception and how the brain processes this nociceptive information.

Woolf later described how the idea for this seminal experiment came to him. Keep in mind that electrophysiologists like Woolf spent their days in tiny, pitch-black rooms, subtly moving electrodes over tissue as they listened to neuronal spike trains like this. So just imagine a man sitting in the dark, pinching rat toes, and listening to intermittent static…and actually learning something. Woolf said:

“I found that most cells responded only to pinch or noxious heat of one or more toes. Some, however, had very large receptive fields encompassing the whole leg and could be driven by innocuous mechanical stimuli… It took me several months of recording to finally realize that [the neurons with large receptive fields] were only recorded at the end of the day, after the repeated noxious stimulation…. This was my ‘eureka’ moment…cells that had somehow changed as a result of the repeated input I had applied.”
Clifford Woolf

In other words, Woolf found that pinching rat toes all day provided just the right kind of repeated noxious stimulation that changed the rules of normal nociception. A toe pinch that evoked a modest withdrawal response in the morning created unexplainably large areas of hind limb hypersensitivity in the afternoon. Incredibly, normal (innocuous) stimuli applied to the hind limb also evoked withdrawal behaviors in the afternoon. He had somehow changed the way spinal interneurons were processing sensation!

If you want to feel a pang of sadness right now, listen to the spike train video again and reflect on your life’s accomplishments.

Deconstructing The Circuit

In science, there is a standard strategy for determining the conditions that are necessary and sufficient for a complex system to produce a behavior (like a rodent producing a “pain” behavior). You systematically inhibit parts of the system and determine whether behavior is affected.

This is like the way you diagnose computer problems: did the power supply die? Is there a loose screw jostling your motherboard? Are any wires frayed? If you replace a cable, is the function restored?

Or the way you troubleshoot a recipe gone wrong: Did you combine the ingredients in the right order? Was the oven preheated? Did you overmix the dough?

Like you, Woolf reasoned that if he wanted to understand the spinal cord’s unique role in pain hypersensitivity, he would need to control other confounding factors that also impact nociception: the brain and peripheral nociceptors.


Nitty Gritty Study Design

If details don’t interest you, skip to the final sections for an overview of study findings.

But if you want to get a strong grasp of mechanisms underlying central sensitization, and if you want to critically interpret the quantitative sensory testing (QST) studies that claim to measure central sensitization, read this section carefully.

Let’s start with the big picture and break down Woolf’s experimental approach:

1. The thermal injury.

One leg of each rat was exposed to 75ºC radiant heat for 60 seconds to create a thermal injury.

Why radiant heat?

When you’re interested in nociception, it’s ideal to have a “pure” stimulus. Radiant heat is appropriate for two reasons:

  • C-fiber nociceptors are responsible for detecting noxious heat, so Woolf knew exactly what type of nociceptor was being activated.
  • He didn’t want other types of sensory neurons to influence his results. A thermode placed on the rat’s skin would be a noxious heat AND pressure stimulus. Radiant heat takes pressure out of the equation. Woolf could then be certain that the subsequent effects would only be caused by C-fiber nociception.

Why 75ºC radiant heat for 60 sec?

I don’t know. This temperature is blistering hot, and a 60 second exposure time sounds brutal. I assume Woolf wanted to create an injury that was severe enough to clearly track the onset and gradual recovery over the next 24 hours.


2. The noxious stimuli.

Hot water.

Hot water very quickly warms the surface temperature of the skin in a uniform way. In contrast, the surface temperature of contact thermodes can sometimes differ from the temperature they are supposed to deliver.

A measure of heat hyperalgesia.

Mechanical stimulation.

To a rat, von Frey hairs pressed against the skin is like someone poking you with the pointy end of an umbrella. Not pleasant. Both the rat and you will quickly withdraw when you are poked.

A measure of mechanical punctate hyperalgesia. (Note: punctate = pinprick, which is considered a subset of tactile  or  pressure  hyperalgesia.)


3. The response.

Animals can’t tell us they are in pain, so we have to rely on their behaviors to infer it. Since Woolf was interested in spine-specific mechanisms, he chose a spinally-dependent behavior. He reasoned that the amount of noxious stimulation needed to produce a withdrawal reflex is also the amount of noxious input that usually gives rise to pain perception. So he narrowed in on the flexion withdrawal response, which is a fancy way of describing a rapid lift of the hind paw.  Flexion is considered a nocifensive (guarding/avoidance) behavior that occurs before nociceptive information can even reach the brain. It’s a reasonable behavioral proxy measure for pain in rats.

Woolf then recorded directly from bicep femoris (lower) motor neurons, which enable flexion withdrawal behavior. Motor neurons are efferent neurons controlled by local spinal circuits. These neurons are responsible for the muscle contractions that withdraw the hindlimb from noxious input.

Specific to spinal cord circuits?  CHECK.

Specific to noxious stimulation?  CHECK.



Brain Be Gone (sort of)

Woolf first sought to determine if the spinal enhancement of nociception required the brain. To do this, he removed the cerebellums of rats (decerebration) in his experiment to accomplish three goals:

  1. Preserve the spinal and brain stem reflex behaviors (like flexion);
  2. Prevent advanced reflex integration by the brain (which can actually exaggerate spinal reflexes because they are no longer inhibited by the brain);
  3. Preserve the rats’ abilities to generate nocifensive behaviors (withdrawal behavior, vocalizations, stimulus orientation), which is necessary to infer that noxious stimuli are intense enough to cause pain.

Woolf wanted to ensure that intact and decerebrated rats showed similar baseline sensitivity (measured by hind limb withdrawal) to the noxious mechanical and thermal stimulation he would use for his experiments. Figures 2.1 and 2.2 confirm this.


2. A low level of neural activity continued after the stimulus stopped. This was the first evidence of stimulus-independent spinal activity, which is also one of the three key features of central sensitization.

When Woolf looked at 25 different biceps femoris motor neurons to see if this was a generalized response, he realized that this ongoing neural activity was steadily increasing over the course of an hour!

Fig 2.4  Neural recordings from 25 motor neurons showed a steady rise in spontaneous neural activity following thermal injury. Adapted from Woolf, 1983.

He noticed that as the ongoing neural activity following the stimulus continued to increase, mechanical sensitivity steadily changed as well.  He wondered…could mechanical (punctate) hyperalgesia somehow be related to the spontaneous activity he was observing?

Fig 2.5  Both the injured hind paw (red) and unaffected hind paw (blue) exhibited mechanical (punctate) hyperalgesia lasting less than 60 minutes after the thermal injury. Adapted from Woolf, 1983.

Identifying the Culprits

Woolf wanted to know how different types of nociceptors were contributing to this effect. He used his knowledge of nerve structure and function to make this happen.

Different types of nociceptors transmit information at different rates (called conduction velocity). These transmission rates are controlled by the diameter of the nerve, which determines how quickly action potentials can be generated and therefore how quickly a nociceptor can fire. C-fiber nociceptors transmit information very slowly because they have small diameters and no myelin to speed up the signal. Nerves encased in myelin (like A-delta nociceptors) transmit information more quickly than unmyelinated C-fiber nociceptors. A-beta touch neurons transmit information most quickly due to their thick myelination. Julius & Basbaum (2001) have an older but still exceptional review of these principles.

Fiber types
Fig 2.6 Structure and function of primary afferent fibers. Adapted from Julius & Basbaum, 2001.


For example, myelinated A-delta nociceptor signals reach the brain more quickly than signals from unmyelinated C-fiber nociceptors. This is why A-delta mediated sharp pain is perceived before C-mediated dull, burning pain: simple differences in travel time.

Woolf decided to differentiate the contributions of different fiber types by looking at time delay signatures. He needed a precise noxious stimulus—in this case, electrical current to the sural nerve (which innervates the biceps femoris). By varying the intensity of this electrical current, he was able to selectively stimulate different groups of sensory neurons and their time delay signatures:

  • A-beta fiber activity was examined with repeated 100 micro-amp currents
  • A-beta and A-delta fiber activity was examined with repeated 250 micro-amp currents
  • A-beta, A-delta, and C fiber activity was examined with repeated 5 mA currents