Temporal Summation of “Second Pain” (TSSP)

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This is a C-fiber-evoked response of dorsal-horn neurons. It is sometimes called “windup”. It is typically tested with a stimulus frequency 0.33 Hz i.e. a stimulation once every three seconds.

Relevance to central sensitization[edit]

It is relevant to understanding central sensitization and at least some forms of chronic pain. Its neural correlates have been studied with fMRI.

Methods of induction[edit]

It can be induced with repeated applications of heat stimuli to the skin of one part of the body. One technique involves finding the temperature that induces moderate pain for a given person and the applying the stimulus repeatedly.

Neural substrate of temporal summation in fibromyalgia[edit]

Regions believed to be involved in this phenomenon are: the ipsilateral and contralateral thalamus, medial thalamus, S1, bilateral S2, mid- and posterior-insula, rostral and mid-anterior cingulate cortex. In a study of TSSP by Staud et al., fibromyalgia patients were more sensitive in that “the stimulus temperatures necessary to evoke equivalent levels of TSSP and corresponding brain activity were less in fibromyalgia patients” than in controls”. The authors summarized their findings by saying that their “results suggest that enhanced neural mechanisms of TSSP in fibromyalgia are reflected at all pain related brain areas, including posterior thalamus, and are not the result of selective enhancement at cortical levels”. (Brain activity associated with slow temporal summation of C-fiber evoked pain in fibromyalgia patients and healthy controls. Staud R, Craggs JG, Perlstein WM, Robinson ME, Price DD. Eur J Pain. 2008 Nov;12(8):1078-89 available online at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582560/.)

Modalities for temporal summation of pain in fibromyalgia[edit]

According to a review by Staud et al. fibromyalgia patients have the following findings related to temporal summation of pain:

  • enhanced TSP
  • longer duration of TSP aftersensations
  • lower stimulus frequency requirements to evoke TSP

Staud’s review (Spatial Summation of Mechanically Evoked Muscle Pain and Painful Aftersensations in Normal Subjects and Fibromyalgia Patients. Roland Staud,1 Euna Koo,1 Michael E. Robinson,2 and Donald D. Price3,4 Pain. 2007 Jul; 130(1-2): 177–187.) of the literature has found that the abnormalities in TSP which been observed in fibromyalgia patients using the following stimulus modalities:

  • heat (Desmeules et al., 2003)
  • pressure/ muscle stimulation (Staud et al., 2003a)

Staud says that repetitive mechanical muscle stimulation was greater than cutaneous heat in fibromyalgia a s compared to normal controls (Staud et al., 2001).

Studies in chronic musculoskeletal pain with pressure algometry using a cuff[edit]

A study by Graven-Nielsen et al. of chronic musculoskeletal pain used “computer-controlled cuff-pressure algometry (pain thresholds and temporal pain summation) on the arm and leg” and also conditioned pain modulation (CPM) by cuff algometry. (Assessment of musculoskeletal pain sensitivity and temporal summation by cuff pressure algometry: a reliability study. Graven-Nielsen T1, Vaegter HB, Finocchietti S, Handberg G, Arendt-Nielsen L. Pain. 2015 Nov;156(11):2193-202.) Results showed that temporal summation of pain was increased in women compared with men (P < 0.05).

Potential utility in testing temporal summation of withdrawal reflexes in fibromyalgia[edit]

According to Arendt-Nielsen this results in an increase in the electro-myographic response that is observed during repeated transcutaneous electrical stimulation (Arendt-Nielsen et al., 1994a). “Compared to healthy controls, fibromyalgia and whiplash pain patients had significant lower thresholds for eliciting the withdrawal reflex during repeated stimulation (Banic et al., 2004).” (Assessment of mechanisms in localized and widespread musculoskeletal pain. Thomas Graven-Nielsen & Lars Arendt-Nielsen, Nature Reviews Rheumatology 6, 599–606(2010), abstract available at: https://www.nature.com/articles/nrrheum.2010.107.)

Role of central sensitization[edit]

According to Graven-Nielsen et al: “Central sensitization has been proposed to occur in patients with whiplash pain and patients with fibromyalgia because the threshold for eliciting the withdrawal reflex based on sequential stimulations was reduced compared with healthy individuals.” (Graven-Nielsen and Lars Arendt-Nielsen, 2010)

Differences between men and women[edit]

Sarlani et al. (2004) found that: “Women exhibit greater temporal summation of heat and mechanically evoked pain.” (Sex differences in temporal summation of pain and aftersensations following repetitive noxious mechanical stimulation. Sarlani E1, Grace EG, Reynolds MA, Greenspan JD. Pain. 2004 May;109(1-2):115-23.)

Relation to aftersensations[edit]

One experimental method that has been used to induce “temporal summation of mechanically evoked pain” as well as “aftersensations following repetitive noxious stimulation” is to apply “[S]ixteen series of 10 repetitive, mildly noxious, mechanical stimuli” to the fingers and then ask subjects to rate “pain intensity and unpleasantness caused by the first, fifth and tenth stimulus in the series, as well as their aftersensations 15 s and 1 min following the end of stimulation”.(Sex differences in temporal summation of pain and aftersensations following repetitive noxious mechanical stimulation. Sarlani E1, Grace EG, Reynolds MA, Greenspan JD. Pain. 2004 May;109(1-2):115-23.)

This causes pain and unpleasantness ratings to increase with repetition of stimulation. Furthermore, this research showed that:

“Temporal summation of pain intensity and unpleasantness ratings were more pronounced in women than men (P<0.0001). In addition, significant temporal summation occurred only with 2 s interstimulus interval for men (P<0.0005) but with 2 and 5 s interstimulus interval for women (P<0.0001). Moreover, women provided greater ratings for the intensity and the unpleasantness of aftersensations (P<0.0005) and reported painful aftersensations at greater frequency (P<0.05)”. (Sex differences in temporal summation of pain and aftersensations following repetitive noxious mechanical stimulation. Sarlani E1, Grace EG, Reynolds MA, Greenspan JD. Pain. 2004 May;109(1-2):115-23.)

Association between temporal summation and aftersensations[edit]

A point of special interest in the Sarlani study seems to be the co-occurrence of aftersensations with temporal summation. In the author’s experience in pressing on fibromyalgia tender points with the Fischer algometer, aftersensations seem to be tied to pain radiation whereby the radiating pain is the aftersensation. It is complicated to rate these aftersensations because the patient needs to be asked after each application of pressure to a tender point a question such as this: “If you have any continued pain after the examiner stops pressing on a spot, say “stop” when it stops and then describe the pain in character and position.” An example might be that they said “stop” after 15 seconds and they say the pain traveled downward or upwards from where the pressure applied for a distance of say 6 inches. It is not clear at this time how to interpret the fine details of what they say, for example it is not clear what to conclude if the pain went down or up, or if it travelled a short distance or a long one. However, in the lab of the author of this Encyclopedia, we got the preliminary general impression that the longer the aftersensation the more severe the problem and the further it travels the more severe the problem. (Perhaps when it travels it could possibly mean that there is lateral stimulation in the brain or spinal cord.)