CT Summation

[Jon Newman]

I thought it would be helpful to start a thread discussing the neurophysiologic concept of summation. A convenient starting place is the wiki entry on the subject. It's short and I'm sure there is more to discuss. For example, is there a distinction between central summation and peripheral summation beyond the anatomic locations of the respective neurons?

[John W]

I'm attaching this 1995 article by Clifford Woolf that discusses the mechanisms of hyperalgesia and touches on temporal summation of peripheral C-fibers resulting in dorsal horn "wind-up."

The intrinsic changes in phenotype expression of neurons is fascinating to me. In particular, the effects of nerve growth factor (NGF) on nociceptor endings resulting in fiber sprouting from the dermis into the epidermis.

It's an excellent review.

[Diane]

Thank you for starting this thread Jon.
I cannot remember learning anything about this before. Not in the context of manual therapy, for sure.
Butler has certainly covered peripheral sensitization thoroughly.

[Diane]

Here is what temporal summation is according to the authors of the sham NDT article (p. 711):

"Temporal summation is a behavioral measure of central sensitization, characterized by the perception of increasing pain intensity to repetitive heat pulses of unchanging temperature provided at a frequency of less than 3 seconds. Temporal summation has not previously been assessed in individuals with CTS to our knowledge; however, individuals with musculoskeletal pain conditions such as fibromyalgia^77,88 and temporomandibular joint dysfunction^78,84 demonstrate greater magnitude of temporal summation than healthy controls. Additionally, temporal summation has been observed to significantly contribute to pain-related disability in individuals with chronic low back pain.³⁹ Consequently, temporal summation appears to be a valid measure of pain sensitivity in other musculoskeletal pain conditions worthy of assessment in individuals with CTS. Temporal summation is a proximal measure of dorsal horn excitability,^23,42,45,67 and inhibition of temporal summation from NDT could represent a mechanism of action for pain relief. We hypothesized that participants receiving NDT would experience greater immediate within-session inhibition of clinical pain, temporal summation, thermal pain threshold, and pressure pain threshold in comparison to those receiving a sham technique. Confirmation of this hypothesis would suggest that NDT elicits a neurophysiological response beyond that of a sham related to hypoalgesia and, in the case of temporal summation, specific to inhibition of dorsal horn excitability across a nerve, as implied by some methods of NDT, has the potential for detrimental effects.^21,22,40,87 Consequently, we monitored neurological status in participants and hypothesized that worsening of neurological status would not be observed in either treatment group."

[Jon Newman]

We were taught about summation in our neuroscience lectures in PT school. According to the 3rd edition of Principles of Neuroscience edited by Kandel, Schwartz, and Jessell:

When synaptic potentials overlap in time, they add together in a process known as temporal summation. In this way individual excitatory postsynaptic potentials that alone might be too small to trigger an action potential can sum to reach threshold. If a postsynaptic cell has a long membrane time constant, the synaptic potential lasts longer and there is more chance for temporal summation. Temporal summation of receptor potentials in receptor cells takes place in a similar fashion.

Temporal summation describes how a nerve responds (its behavior, not the person's) to repetitive stimulus. The above paragraph also draws a distinction between temporal summation of postsynaptic potentials and temporal summation of receptor potentials. Temporal summation of postsynaptic potentials is what is being referenced in the article.

Do I have that right?

[Jon Newman]

In the excellent resource Pain: New Essays on Its Nature and the Methodology of Its Study, Murat Aydede and Don Price author a chapter titled The Experiential Use of Introspection in the Scientific Study of Pain and Its Integration with Third-Person Methodologies: The Experiential-Phenomenological Approach. Got that?

From that chapter:

...summation must occur with the spinal cord dorsal horn, because similar experiments conducted on peripheral A- and C-nociceptors show that their responses do not increase with stimulus repetition (Price, 1977). Thus, temporal summation of second pain depends on mechanisms of the central nervous system (i.e. dorsal horn neurons) not changes in peripheral receptors.

These psychophysical-neural parallels have been confirmed not only in the case of single neurons of the spinal cord but also in the case of neural imaging at the level of the somatosensory region of the cerebral cortex (Tommerdahl et al., 1996).

[Jon Newman]

Here are some definitions that are related to what we're discussing and good to understand in general.

From the IASP:

Pain Threshold
The least experience of pain which a subject can recognize. Note: Traditionally the threshold has often been defined, as we defined it formerly, as the least stimulus intensity at which a subject perceives pain. Properly defined, the threshold is really the experience of the patient, whereas the intensity measured is an external event. It has been common usage for most pain research workers to define the threshold in terms of the stimulus, and that should be avoided. However, the threshold stimulus can be recognized as such and measured. In psychophysics, thresholds are defined as the level at which 50% of stimuli are recognized. In that case, the pain threshold would be the level at which 50% of stimuli would be recognized as painful. The stimulus is not pain (q.v.) and cannot be a measure of pain.

Pain Tolerance Level
The greatest level of pain which a subject is prepared to tolerate. Note: As with pain threshold, the pain tolerance level is the subjective experience of the individual. The stimuli which are normally measured in relation to its production are the pain tolerance level stimuli and not the level itself. Thus, the same argument applies to pain tolerance level as to pain threshold, and it is not defined in terms of the external stimulation as such.

[Jon Newman]

Section 4.4 (from the same book and chapter referenced in post #6) is titled The Significance of Parallels between Pain Phenomenology and Central Neural Activity. In this section Price and Aydede make it a point to highlight that the subjective experience of pain, the sensory qualities, are the end result of the characteristics of the stimulus (duration, intensity, frequency), the transducing ability of the receptors (chemical, thermal, mechanical) and, importantly, "on integrative mechanisms of the central nervous system."

..there is nothing about the physical properties of heat taps or even the physiological characteristics of peripheral C-nociceptors that would allow someone to predict temporal summation of second pain....Sensory and affective qualities of pain covary with patterns of neural activity in the central nervous system and not just the physical characteristics of the stimuli. Give this high variability between stimulus characteristics (or, features of the peripheral nervous system) and qualities of the resulting subjective experience, it is very clear that the relationship between these qualities of pain experience and neural activity can be explored only through careful analysis of both subjective experience and neural activity. It should by now be obvious that drawing on introspection is an indispensable condition of such an exploration.

This commentary is consistent with the previous post's cautions about conflating pain and stimulus. It also brings up the question, "what are the introspective characteristics of favorable outcome (assuming there are some) given that we aren't monitoring neural activity in the clinic but rather introspective judgements?"

[Jon Newman]

So does anyone do heat taps (to test for temporal summation) in the clinic with their patients?

It doesn't seem like this would be particularly difficult and does seem to provide some information about the state of the state of the nervous system.

[Jon Newman]

Here are three different methods for determining temporal summation of thermal stimuli used by the authors in three different studies (not the exact same authors for every experiment).

A train of 10 consecutive heat pulses, of less than 1-second duration, at an interstimulus interval of 3 seconds, was delivered to the thenar eminence of the participants’ dominant hand. Participants were asked to rate their second pain intensity associated with all 10 heat pulses, and temporal summation was defined as the difference between the fifth and second pain rating for purposes of our analysis.(Source)

Temporal summation assessment used previously established protocols to observe pain perception to 10 heat pulses at 51°C, applied to the thenar surface of the palm of the hand with an interstimulus interval of 0.33 seconds...Temporal summation was calculated by the average pain rating of the first 5 heat pulses for purposes of our data analyses.(Source)

A train of 10 consecutive heat pulses of <1 second duration at an inter-stimulus interval of .33 Hz was delivered to the subjects. A frequency of .33 Hz was selected to ensure the development of temporal summation [28]. The temperature of the heat pulses rapidly fluctuated (10°C/sec) from a low of 35°C to a peak of 47°C. The research assistant recorded NRS ratings of pain intensity. Subjects were asked to rate their delayed (second) pain intensity associated with the first, third, and fifth heat pulses. These ratings are believed to be primarily mediated by C-fiber input (Source)

I wanted to compare how temporal summation varied across the three experiments to see if I could spot any trends. However, the variation between these different assessment methods leaves me a little unclear about how to best characterize temporal summation of thermal stimuli and I'm not sure my efforts would be informative given the variation.

Actually, I have a number of technical questions that I'm trying to answer through reading a bit more.

[Frédéric]

I just wanted to be sure I get this right.

Temporal summation is really of peripheral origin and starts because of a lasting (nociceptive and intense) stimulus.

Any central processing (by efferent brain pathways) upregulating a pain state are not the temporal summation we are talking about here.

So in a central sensitization state, temporal summation could be the means by which the external stimulis affected the CNS by creating the initial increased sensitivity. On top of this phenomenon, the up/downregulating pathways of the brain either increased or decreased the sensitization of the CNS creating the patient's observed sensitivity state.

The way I understand it, temporal summation could be the initial wind up of the CNS ultimatly leading to central sensitization.

Do I get it right ?

[Frédéric]

Do psychosocial issues (like stress) yields the CNS a higher sensitivity for temporal summation?

[Frédéric]

In a PPP how do we differentiate a problem mostly because of temporal summation (more of nociceptive origin) from a problem of a more central neurogenic origin (with little or no nociception stimuli ) ?

Both could have the same allodynia/hyperalgia feature, right ?

[Jon Newman]

Hi Frédéric,

Maybe someone has access to this article

Price DD, Hu JW, Dubner R, Gracely RH. Peripheral suppression of first pain and central summation of second pain evoked by noxious heat pulses. Pain 1977;3:57–68. PubMed: 876667

My understanding is that temporal summation is the name given to an observable, repeatable phenomena.

Originally Posted by Kharma44

In a PPP how do we differentiate a problem mostly because of temporal summation...

Temporal summation reveals something about the sensitivity of the CNS--the stimulus (10 quick heat pulses) is the proximal contributor to the current state of the CNS but not the cause of its (trait?) sensitivity.

Originally Posted by Kharma44

Do psychosocial issues (like stress) yields the CNS a higher sensitivity for temporal summation?

Anything that sensitizes the CNS, and especially the DRG, would (I think) result in an amplified pain response to 10 quick heat pulses relative to someone without so much sensitivity. But I could be wrong. See below.

Originally Posted by Kharma44

Any central processing (by efferent brain pathways) upregulating a pain state are not the temporal summation we are talking about here.

I don't know enough to confidently answer. As I said above, I would expect that a central nervous system sensitized to nociception, regardless of mechanism, would demonstrate an amplified pain rating to 10 quick heat pulses relative to someone with less sensitivity. However, perhaps a sensitized DRG in particular is a necessary and sufficient condition for the amplified pain response. To put it differently, it is possible that you would not see an amplified pain response to 10 quick heat pulses in the absence of a sensitized DRG.

I keep emphasizing "amplified" because I believe it is normal to have an increased pain experience to repeated application of nociceptive stimuli and that it is the magnitude of the responses that we compare for degree of sensitivity or for the effectiveness of an intervention. That was my concern in my previous post. If we're comparing changes in the magnitude of a response, it seems important that we're capturing that data in a consistent manner and that is being done within the single studies I posted. However, the difference between the fifth and second pain rating is going to result in a different magnitude than the average pain rating for the first five impulses making comparisons across multiple studies quite difficult for the home enthusiast.

[Diane]

I did some digging on scholarpedia about temporal summation. There were 35 hits from there. Perhaps they will be useful to someone else. I don't have time to dig deep into this today, but I can put it on the to-do list.