The temporal dynamics of pain

The dynamics of pain: Evidence for simultaneous site-specific habituation and site-nonspecific sensitization in thermal pain – J Pain. – free full-text PMC article – 2015 Jul

People ask me: “If you have pain all the time, don’t you just get used to it?”

I used to wonder that myself because I respond to non-painful sensations, like wearing a watch, this way all the time. By contrast, any repetitive even slightly painful stimulation, like wearing too-tight shoes, makes me “allergic” to it: each repetition becomes more painful.

I’ve always been aware that I develop increasing sensitivity to repeated site-specific mild pain, which this article suggests is due to the “disturbed pain-adaptation processes” of chronic pain.

“Patients with several chronic pain conditions (e.g., fibromyalgia, migraine and chronic back pain) show reduced habituation, or abnormal sensitization instead of habituation, to repeated noxious stimuli”

EDS pains could be classified into both groups in this article: site-specific pains and pains in multiple sites (site-nonspecific). We have our consistently troublesome areas, like the sacroiliac joint, and simultaneously have the same pain sensation (ache, stab, burn, etc.) in multiple other joints.

Repeated exposure to noxious stimuli changes their painfulness, due to multiple adaptive processes in the peripheral and central nervous system.

Somewhat paradoxically, repeated stimulation can produce an increase (sensitization) or a decrease (habituation) in pain.

Adaptation processes may also be body-site-specific or operate across body sites, and considering this distinction may help explain the conditions under which habituation vs. sensitization occurs.

To dissociate the effects of site-specific and site-nonspecific adaptation processes, we examined reported pain in 100 participants during counterbalanced sequences of noxious thermal stimulation on multiple skin sites

Analysis of pain ratings revealed two opposing sequential effects:

repeated stimulations of the same skin site produced temperature-dependent habituation, whereas

repeated stimulations across different sites produced sensitization

Stimulation trials were separated by ~20 seconds and sensitization was unrelated to the distance between successively stimulated sites, suggesting that neither temporal nor spatial summation occurred

To explain these effects, we propose a dynamic model with two adaptation processes, one site-specific and one site-nonspecific. The model explains 93% of the variance in the group-mean pain ratings after controlling for current stimulation temperature, with its estimated parameters showing evidence for habituation for the site-specific process and sensitization for the site-nonspecific process

The two pain-adaptation processes revealed in this study, and the ability to disentangle them, may hold keys to understanding multiple pain-regulatory mechanisms and their disturbance in chronic-pain syndromes.

This article presents novel evidence for simultaneous

  1. site-specific habituation and
  2. site-nonspecific sensitization in thermal pain

Introduction

Pain perception is strongly modulated by dynamic adaptive processes.

Although the degree of pain is driven by the intensity of a noxious stimulus, there is also a substantial portion of variance arising from temporal adaptation processes that may or may not interact with stimulus intensity.

Many chronic-pain syndromes are characterized by disturbed pain-adaptation processes, such as a lack of habituation or abnormal sensitization e.g., which may reflect an increased excitability of central and/or of peripheral nociceptive neurons.

The temporal dynamics of pain, and the ability to estimate them accurately, may hold keys to understanding multiple mechanisms of pain regulation, as well as the development of chronic pain

There are well-known dynamic effects in pain that occur during continuous or fast repetitive noxious stimulation, such as temporal summation and offset analgesia (the disproportionately large decrease in thermal pain following a slight decrease in stimulus temperature)

Temporal pain adaptation also occurs during sequences of more widely spaced noxious stimuli (e.g., separated by 10–80 seconds). Several studies have reported a rapid decrease in experienced pain over the course of such stimulus series, although increases in pain over time have also been reported.

As is common in the pain literature, we will use the terms ‘habituation’ and ‘sensitization’ to refer to the general class of adaptive processes whereby current experienced pain is decreased or increased (respectively) by previous painful stimuli.

One important factor that affects which pain-adaptation processes predominate during repeated exposure to noxious stimuli may be whether these stimuli are applied to the same or to different body sites.

Although it has been argued that site-specific and site-nonspecific effects reveal peripheral versus central adaptation processes, respectively, this is not necessarily true: although pain-adaptation effects that occur during successive stimulations of different body sites must indeed originate in the central nervous system, changes in pain produced by repeated stimulation of the same skin site can be either peripheral or central in origin

One hundred healthy participants completed the experiment

Much of the variation in pain report is driven by variation in noxious stimulus intensity, but substantial adaptation effects—sequential effects of the stimulation history—can also strongly modulate pain. Adaptation effects include both habituation and sensitization across time, and may vary in their direction and magnitude across individuals

Discussion

Site-specific habituation in this study depended on stimulus intensity in two ways:

  1. More-intense stimuli produced stronger habituation for subsequent stimulations on the same skin site, but
  2. more-intense (48–49°C) stimuli also reversed the habituation effect on the current trial,

resulting in sensitization for the highest-intensity stimuli (more current pain for stimulations on previously stimulated sites).

By suppressing mild repeated pain, while still allowing more biologically salient stimuli – which may, e.g., signal tissue damage – to get through, habituation for low- and sensitization for high-intensity current stimuli may serve an important adaptive role in optimizing survival behavior.

Disturbed pain-adaptation processes play a key role in the pathophysiology of chronic pain.

Patients with several chronic-pain conditions (e.g., fibromyalgia, migraine and chronic back pain) show reduced habituation, or abnormal sensitization instead of habituation, to repeated noxious stimuli, which is reflected in both their subjective pain and pain-related brain activation.

Whether deficient pain habituation is a pre-dispositional factor that contributes to the development and/or persistence of chronic pain, or the result of an altered cortical state caused by the chronic pain is a matter of debate

As is usual, the direction of cause and effect cannot be distinguished even though they can be demonstrated to interact with each other.

Although most of our participants showed site-specific habituation and site-nonspecific sensitization, this was not the case for everyone (see

Thus, even within the healthy population there is considerable inter-individual variability in the temporal dynamics of pain. These individual differences may reflect inter-individual variability in the sensitivities and/or decay rates of the site-specific and site-nonspecific adaptation processes

A recent study examining the effects of repeated noxious thermal stimulation over the course of several days also found remarkable individual differences in pain adaptation: half of the participants showed habituation and the other half showed sensitization of their pain ratings

Furthermore, those who sensitized, but not those who habituated, showed a reduction in grey matter density in several pain-processing brain regions on the last compared to the first stimulation day. Interestingly, similar reductions in grey matter density have been reported in chronic-pain patients, suggesting that pain sensitization (in this case across several days of noxious stimulation) may indicate an increased risk for chronic-pain development

Although our results provide strong evidence for the existence of two distinct and opposing pain-adaptation processes, the biological basis of these processes remains to be explored in future studies. The site-nonspecific sensitization effect most likely reflected central mechanisms, especially given its independence on the distance between successive stimulation sites. The site-specific habituation effect, on the other hand, could reflect peripheral and/or central processes.

It remains to be explored whether the distinct effects of site-specific and -nonspecific repetition generalize to other types of pain—e.g., mechanical and electrical—and to other repetition rates.

A recent study showed that experienced pain during longer series of repeated heat stimuli applied to the same skin site follows a bi-phasic time course, with initial habituation followed by sensitization

This might explain my response if the “initial habituation” only lasts a few seconds. I just transition almost immediately to the sensitization phase.

Whether or not these two effects arise from the same underlying processes, and whether they can be predicted by our dynamic model, are interesting questions for future research.A


A description of “Neural Adaptation” from Wikipedia:

Neural adaptation or sensory adaptation is a change over time in the responsiveness of the sensory system to a constant stimulus.

It is usually experienced as a change in the stimulus.

For example, if one rests one’s hand on a table, one immediately feels the table’s surface on one’s skin. Within a few seconds, however, one ceases to feel the table’s surface.

The sensory neurons stimulated by the table’s surface respond immediately, but then respond less and less until they may not respond at all; this is an example of neural adaptation.

Neural adaptation is also thought to happen at a more central level such as the cortex

Fast and slow adaptation

Fast adaptation occurs immediately after stimulus presentation i.e., within 100s of milliseconds. Slow adaptive processes that take minutes, hours or even days.

The two classes of neural adaptation may rely on very different physiological mechanisms.

While large mechanosensory neurons such as type I/group Aß display adaptation, smaller type IV/group C nociceptive neurons do not.

As a result, pain does not usually subside rapidly but persists for long periods of time; in contrast, one quickly stops receiving touch or sensory information if surroundings remain constant.

Habituation vs adaptation

The terms neural adaptation and habituation are often confused for one another.

Habituation is a behavioral phenomenon while neural adaptation is a physiological phenomenon, although the two are not entirely separate.

During habituation, one has some conscious control over whether one notices something to which one is becoming habituated. However, when it comes to neural adaptation, one has no conscious control over it. For example, if one has adapted to something (like an odor or perfume), one can not consciously force himself to smell that thing.

Neural adaptation is tied very closely to stimulus intensity; as the intensity of a light increases, one’s senses will adapt more strongly to it. 

In comparison, habituation can vary depending on the stimulus.

With a weak stimulus habituation can occur almost immediately but with a strong stimulus the animal may not habituate at all (a cool breeze versus a fire alarm).

Habituation also has a set of characteristics that must be met to be termed a habituation process.

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2 thoughts on “The temporal dynamics of pain

  1. Laura P. Schulman, MD, MA

    This is really interesting. I wonder, though, whether the responses of “healthy subjects” can be taken as equivalent to those of actual chronic pain sufferers?

    Given the recent experiences of both myself and friend blogger Kara, of “Polishing Dookie,” I see a pattern where both of us are so accustomed to pain as a constant companion, that each of us separately ignored an intensification of our “baseline” pain, thinking it was just more of the same, having been punished by the medical system for complaining. In my case, the pain was due to a bone that had died and crumbled, and tendons that had frayed. Hers was due to a ruptured bowel. She has barely clawed her way back from death, six weeks mostly living in the ICU. We get so used to just slogging through this sea of pain all the time, it’s hard to know when to actually worry about it. That’s why I wonder about the validity of applying data on pain that use “normal” volunteers.

    What do you think?

    Liked by 1 person

    Reply
    1. Zyp Czyk Post author

      I agree with you.

      “Normal” people process any physical stimulus differently than people who have been living with constant pain for years. Our nervous system has developed what I think of as “ruts” that facilitate more efficient transmission of pain signals, so it’s a lot “easier” for us to feel pain.

      All studies of pain are suspect because there can never be a control group. Plus, imagine a long-term opioid trial where half of the people suffering in misery are given a placebo – an ethical nightmare.

      But that probably wouldn’t concern the researchers. It doesn’t seem like anyone studying pain has any ethical concerns these days.

      Liked by 1 person

      Reply

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