This paper (Parts I and II) reviews the measures employed in studying the brain neurophysiological activities of clinical pain. In Part II, these measures include the imaging and measurement of brain blood flow and hemodynamics in various regions of the brain, the scanning of gross and fine brain structures by computerized axial tomography or magnetic resonance imaging, and the imaging and measurement of brain metabolic changes, energy uptake, and receptors bindings through positron emission tomography or single-photon emission computerized tomography. Molecular chemical transformation by the nuclear magnetic resonance analysis of tissue changes and analgesic-receptor interactions is also noted. Most studies of the cerebral measures of traumatic and pathophysiological pain reported in the literature are concerned with headache. The relationships of brain activities among sensory processes of nociception, subjective experience of pain intensity and quality, emotional reaction, and cognitive coping often are complex and not well elucidated in man. Although significant changes in the cerebral physiological parameters are frequently reported in pain patients, the specificity and sensitivity of these measures as objective markers for human pain, reviewed from Part I and Part II together, has not yet been conclusively defined. Also, normative data basis and criteria for classifying abnormality of these brain measures must be established and their validity and reliability be carefully examined so that they can be confidently applied in diagnosis and management of clinical pain. Nevertheless, advancement on measurement of temporal dynamics in 3-D topographic mapping of cortical activities and source localization modeling, together with tomographic imaging of neurochemical metabolisms in the brain will further our scientific understanding of cerebral pain mechanisms. A window on the brain of human pain is being opened.

Human brain measures of clinical pain: a review I. Topographic mappings

Identification of pain, intensity and P300 components in the pain evoked potential.

Long latency brain potentials were evoked by infrared laser stimuli (LEPs) applied to the right forehead in order to activate the thinnest cutaneous A-delta afferents of the upper branch of the trigeminal nerve thus inducing a painful sensation. Ten healthy male subjects participated in 4 identical subsequent sessions, one week apart, receiving 4 blocks of 40 stimuli each. This way the individual trigeminal LEPs, as well as their inter- and intrain-dividual reliability were determined. Five major components could be identified, denoted by polarity and peak latencies: N150, P230, N300, P360, N480. The LEP waveforms were found to be highly stable within subjects, peak latencies varied by less than 5%. Great variation in waveform appeared amongst subjects, peak latencies varied by more than 15%. The last two components exhibited the largest variability and were not identified in all subjects.

Laser evoked brain potentials in response to painful trigeminal nerve activation.

Heterotopic painful stimulation decreases the late component of somatosensory evoked potentials induced by electrical tooth stimulation

Dental somatosensory evoked potentials (SEPs) corresponding to the stimulus intensity levels were recorded at 6 different levels of intensity presented in a randomized order. The relationships between the amplitude of the late SEP component with latency between 150 and 300 msec and each stimulus intensity level were also compared in conditions of randomized intensity and constant intensity. The amplitude of the late component increased significantly with the increased stimulus intensity both in the randomized and constant intensity stimulation. The amplitude of the late component in the randomized stimulation with a 1-sec interstimulus interval (ISI) increased in the same manner as that in the constant intensity condition with a 1-sec ISI. The randomized stimulation with the prolonged ISI increased the amplitude of the late component. The latency of the late positive component significantly increased with the randomized stimulation with a 3-sec ISI. This phenomenon might be attributable to the psychological contamination. SEP recording in the randomized dental stimulation with a 1-sec ISI may have applications in neuropharmacological research or physiological research on pain and evaluation of the effects of analgesics, anesthetics, acupuncture and transcutaneous electrical nerve stimulation (TENS).

A new method of recording somatosensory evoked potentials by randomized electrical tooth stimulation with 6 levels of intensity

The relationship between the amplitude of somatosensory evoked potentials (SEP) and the subjective pain estimation using a visual analogue scale (VAS) was examined in 8 volunteers undergoing randomized electrical tooth stimulation with 3 different intensities. Randomized stimulation was used instead of repetitive stimulation with a fixed intensity in order to minimize the phenomena of habituation and expectancy in recording the SEP and VAS. The VAS scores increased significantly with the stimulus intensity. The amplitude with a latency between 160 and 300 msec (N160-P300) showed a significant increase with the increased intensity. But the amplitudes between 60 and 110 msec (N60-P110) and between 110 and 160 msec (P110-N160) showed no significant change. There was a significant correlation between the amplitude of N160-P300 and the VAS scores. These findings indicate that the component between 160 and 300 msec reflects the perceived pain intensity and the psychological evaluation processes such as cognition, meaning, interpretation and appreciation of pain. The method of randomized stimulation can serve as a simple and useful way for the objective or subjective pain estimation.

Haruo Sano

Papers

Relationship between subjective pain estimation and somatosensory evoked potentials by electrical tooth stimulation.