COMUNICACIÓN CIENTÍFICA Y POLÍTICA CIENTÍFICA:

Recent neuroscientific accounts of hypnotic analgesia have mainly argued that it repre-sents either (1) a specific kind of distraction or (2) a phenomenon during which normal information processing becomes disrupted or disorganized due to a significant dissocia-tion of neural communicadissocia-tion between brain areas.

4.3.1 Hypnotic analgesia—a specific form of distraction?

From an information processing viewpoint, hypnotic analgesia has been conceptualized as a specific form of attention modulation, i.e. as a state of divided attention where subjects become distracted from pain by simultaneously allocating all attentional resources to the ongoing suggestions of hypnotic analgesia (Crawford et al. 1993, 1998;

Crawford 1994). This manipulation of attention was thought of as dynamically changing the neural interactions between subcortical and prefrontal areas of the brain (Crawford 1994). While the fronto-limbic attentional system was conceived to attenuate the processing of noxious input transmitted from thalamic relay nuclei to cerebral struc-tures, the prefrontal cortex was implicated to inhibit thalamo-cortical neural projections (Birbaumer et al. 1990). A further crucial role of thalamo-cortical structures in attention was also emphasized by models on the existence of a central attentional capacity system

(Posner and Petersen 1990). According to this idea, hypnotic suggestions are thought to act as verbal stimuli that pull subject’s attention towards the auditory input and its processing and apart from the processing of noxious input. This shift of attention from the somatosensory input channel to the auditory channel is thought to be one of the most significant and crucial mechanisms of hypnosis-induced pain control (Hilgard and Hilgard 1983). Based on these considerations, it was suggested that hypnotic analgesia and distraction of attention might share similar, if not the same, brain mechanisms.

However, recent studies on brain electrical neural activities in humans during hypnotic analgesia and distraction from painful stimulation have shown that this conception might be misleading. In two studies, the effects of distraction and hypnotic analgesia on pain ratings and the information processing of the brain to noxious stimulation were investigated by recording subjects’ pain ratings to several hundred noxious stimuli and somatosensory evoked potentials (SEPs) of the brain in response to these stimuli. The analysis of SEPs represents a well-established method for the investigation of noxious information processing and the identification of brain mechanisms associated with the experience of pain. Late components of SEPs in response to noxious electrical, mechani-cal, thermal or laser heat stimuli normally show biphasic waveforms with a negative deflection of about 150 ms in response to an electrical stimulus, called N150 or N200 in the case of laser heat stimulation (also called laser-evoked potentials, LEPs). With electri-cal stimulation, this negative waveform is immediately followed by a positive deflection at about 260 ms post-stimulation, whereas a similar positive waveform occurs at about 320 ms (P320) in the case of the LEP. This shift of peak amplitudes indicates that the latencies of most SEP amplitudes are sensitive to the stimulus modality used and to the speed by which the afferent neural fibres conduct the information from the stimulus site to the brain. The magnitude of peak-to-peak-measures of these late SEP components, i.e. the N150/P260 or the N200/P320, was found to be significantly correlated with the physical intensity of the stimulus applied (Bromm and Scharein 1983) and even more with subjects’ reports on the intensity and aversiveness of stimulation (e.g. Flor et al.

1992). The stronger the physical stimulus was perceived, the larger were these peak-to-peak magnitudes. Similar positive correlations between peak-to-peak-to-peak-to-peak measures and both physical stimulus intensity and pain report were reported for noxious electrical tooth-pulp stimulation, laser stimulation and electrical intracutaneous stimulation. Partial correlation analysis between event-related potential (ERP) measures (peak-to-peak amplitudes or baseline-to-peak of SEP components), physical stimulus intensity and pain report furthermore confirmed that the magnitude of the ERP measures is more closely related to the subjective experience of pain than to the physical intensity of stimu-lation (Chen et al. 1979). Due to this observation, it was suggested that these late ERP components primarily represent correlates of cognitive and evaluative stimulus process-ing and less probably reflect physical properties of the stimulus input (Miltner and Weiss 1998). Due to this reason, a number of studies have used these ERP measures for the evaluation of different methods of pain control. In many studies, it was demonstrated that these ERP amplitudes were significantly smaller when the pain treatment in question significantly affected a subject’s pain as compared with placebo methods that

had no effect on a subject’s pain (e.g. for pharmacological treatments, see Bromm and Lorenz 1998; for psychological interventions such as distraction of attention, see Miltner et al. 1989; Friederich et al. 2001; for hypnotic analgesia, see Sommer 1966; Arendt-Nielsen et al. 1990; Miltner et al. 1992; Friederich et al. 2001).

In the first study of our group on the effects of hypnotic analgesia as compared with distraction, a group of 26 high suggestible subjects was selected from 200 undergraduate students according to their hypnotic suggestibility assessed by the Barber Suggestibility Scale (BSS) and the Harvard Group Scale of Hypnotic Susceptibility (HGSHS: A).

Additionally, subjects were tested in a cold pressure test before and after receiving a glove analgesia induction. Subjects were accepted for the experiment proper where they were able to maintain their hands for at least 100 s in ice water with a constant temperature of about+4°C while being exposed to hypnotic glove analgesia. Twelve subjects fulfilled this criterion and volunteered to take part in this experiment. After being familiarized with the experimental setting and determination of each individual’s pain threshold to electrical intracutaneous stimuli (IES; Bromm and Meier 1984), subjects were exposed in a counterbalanced sequence to three experimental conditions during each of which they received three series of 20 painful IES. The three experimental conditions included a con-trol condition without any intervention (CC), a condition with suggestions of hypnotic analgesia (HA) and a distraction of attention (DA) condition where the subject’s atten-tion was distracted away from the stimulaatten-tion. After each block of stimulus presenta-tions, subjects were requested to rate the intensity and aversiveness of pain on a visual analogue scale (VAS). During the control condition, subjects were asked to sit silently in their experimental chair and stay in a relaxed state. In condition HA, hypnotic sugges-tions were given by an experienced hypnotherapist. After the induction of hypnosis, sub-jects received suggestions that they would wear anaesthetic gloves that cause the sensations of their middle finger tip to become absolutely numb and totally insensitive to any kind of pain. During the DA condition, subjects received a word puzzle task. They had to find words from a conglomerate of letters organized in crossword puzzle style.

During all conditions, subjects sat in a reclining chair in an electrically shielded, sound-attenuated room, and brain electrical activities to ICE were recorded from a dense array of electrodes. When subjects were exposed to suggestions of hypnotic analgesia as com-pared with the control condition without intervention, subjects’ pain intensity ratings were significantly reduced, with values partially below the pain threshold. Similarly, pain ratings were also significantly lower during the distraction instruction as compared with the control condition. No significant difference for pain intensity ratings was found between the hypnosis and the distraction condition, indicating that both instructions affected subjects’ pain intensity similarly. Also, the aversiveness of stimuli was signifi-cantly affected by hypnotic analgesia, with stimuli being rated as less aversive during hypnotic analgesia and distraction as compared with the control condition (see Fig. 4.1)

During all three conditions, the SEP showed three major components at the vertex of the subject’s head (see Fig. 4.2): a positive component at 60–100 ms post-stimulus (P80), a negative component at 100–180 ms (N150) post-stimulus and a positive component at 150–300 ms (P260) post-stimulus. Additionally, a positive component at 300–400 ms

post-stimulus (P300) was detected at Pz. While comparisons of latencies of these compo-nents and for the magnitude or topography of earlier compocompo-nents of the SEP (~80 ms) showed no significant differences between conditions, the comparisons of late SEP amplitudes revealed significant differences between the three experimental conditions.

The most relevant finding was that the peak amplitude of the positive brain electrical activity at around 260 ms post-stimulus was significantly lower during distraction as

Fig. 4.2 Event-related potentials at electrode Cz in response to intracutaneous electrical stimulation during a control situation, suggestions of hypnotic analgesia, and distraction of attention.

The components investigated are marked.

N150

P260

Rest Distraction Hypnotic Analgesia

1000 500

ms 0

P80

−5

+5 µV CZ

Fig. 4.1 Pain intensity and pain aversiveness ratings on a visual analogue scale (VAS) in response to intracutaneous electrical stimulation during a control situation, suggestions of hypnotic analgesia and distraction of attention.

8

6

4

VAS units

2

0

Control Hypn. Analg. Distraction

Intensity Aversiveness

compared with hypnotic analgesia and the control condition, but no significant differ-ences were found for the magnitude of this component between hypnotic analgesia and the control condition. Similar results were also seen for components at around 300 ms post-stimulus and thereafter.

Results from this study clearly indicate that suggestions of hypnotic analgesia and dis-traction of attention significantly affect subjects’ feelings of pain when stimulated painfully with electrical stimuli. Stimuli rated as painful and aversive during a control condition turn into stimuli rated as less painful and less aversive during both hypnotic analgesia and distraction from stimulation. This difference between hypnotic analge-sia/distraction and the control condition occurred in spite of the fact that the physical strength of stimuli was kept constant throughout all three experimental conditions.

Therefore, the present investigation confirms earlier reports that hypnotic analgesia (Halliday and Mason 1964; Hilgard and Hilgard 1983; Miltner et al. 1992; Peter, 1998;

Friederich et al. 2001) and distraction of attention (Miltner et al. 1989; Johnson et al.

1991; Friederich et al. 2001) represent effective methods for the control of acute experi-mentally induced pain.

In this second study (Friedrich et al. 2001), these observations were further tested with 220 young healthy student volunteers. Prior to the experiment proper, subjects again were examined for hypnotic susceptibility using a German version of the Harvard Group Scale of Hypnotic Susceptibility: Form A (HGSHS: A) and the German version of the Stanford Hypnotic Susceptibility Scale: Form C (SHSS: C). From this sample, 15 highly hypnotizable subjects aged 19–30 years with high HGSHS scores (9–12) and additional high scores in the SHSS (9–12) participated in the experiment proper. Its main session again consisted of three experimental conditions counterbalanced across subjects: (1) a control condition where subjects were instructed to rest; (2) a condition of hypnotic analgesia where subjects received hypnotic induction and then suggestions for glove analgesia and instructions for relaxation imagery (i.e. walking on a beach); and (3) a con-dition where subjects’ attention was distracted by listening to a tape recording of a short crime story. Subjects were told that they would have to recall as many details of this story in a subsequent memory test and that a bonus will be paid for good recall. During each condition, subjects were stimulated with noxious heat laser stimuli. After each block of 10 stimuli, the subjects were requested to rate the average intensity and aversiveness of the 10 preceding stimuli. During each experimental condition, 70 stimuli were applied with a constant laser energy evoking a subjective perception of moderate pain (for more methodical details, see Weiss et al. 1997; Weiss and Miltner 2006). During the whole experiment proper, LEPs were obtained from 62 electroencephalography (EEG) electrode sites.

Results of the behavioural data were similar to those of study 1. Ratings of pain intensity and pain aversiveness were significantly reduced, with values below the pain threshold when subjects were exposed to suggestions of hypnotic analgesia or to the distraction condition as compared with the control condition. During all three conditions, LEPs showed two major components, i.e. the N200 and P320, respectively. Again, the N200 magnitude to laser heat stimuli was significantly reduced while subjects were requested

to distract their attention from stimulation as compared with hypnotic analgesia, while no significant differences were found between hypnotic analgesia and the control condi-tion and between the control and distraccondi-tion condicondi-tion. The P320 amplitude was signifi-cantly reduced during distraction as compared with the control condition and with hypnotic analgesia, while no significant difference was found when hypnotic analgesia was compared with the control condition. The same pattern of results was obtained when the analysis was based on peak-to-peak measures representing the magnitude of the N200–P320 complex.

Like the previous study, this study also clearly reveals that suggestions of hypnotic analgesia significantly affected subjects’ feelings of pain when they were stimulated with moderately painful stimuli. These remarkable subjective effects of distraction are also confirmed by the observations of late ERP amplitudes that again were significantly reduced as compared with the control condition. This finding confirms earlier studies by Miltner et al. (1989) and Yamasaki et al. (1999). When the brain electrical activities and its SEP amplitudes to the experimental stimulation are considered as additional indicators for the effectiveness of analgesic procedures, the data of this study confirm that distrac-tion represents an effective method of pain control. During distracdistrac-tion, we found signifi-cantly reduced magnitudes of the N150–P260 complex as well as of the P260 and P300 components as compared with hypnotic analgesia and, in part, as compared with the control condition. This finding confirms earlier studies (e.g. Miltner et al. 1990, Yamasaki et al. 1999; Friederich et al. 2001) and points to the option that filters at thalamic and thalamo-cortical levels are activated during distraction so as to prevent or to protect the somatosensory cortices from noxious input. In contrast, our analyses of ERP compo-nents did not reveal similar results on the size of the late ERP compocompo-nents for hypnotic analgesia. When highly suggestible subjects were exposed to suggestions of hypnotic analgesia, late ERP amplitudes in both studies were not reduced but actually tended to show even larger magnitudes than during the control condition. This difference clearly indicates that hypnotic analgesia acts on the brain in a different manner than distraction.

According to these observations, it appears as if the somatosensory cortex and associated cortical areas still receive full information about the noxious input and that this process-ing of information is not affected by the suggestions of analgesia. However, our subjects reported that the laser stimulation was perceived as less painful during hypnotic analge-sia than the stimulation during the control condition, although in both conditions the stimulus type and its physical intensity were kept constant. This observation is consistent with suggestions by Hilgard and Hilgard (1983) that hypnotic analgesia is characterized by a dissociation of the processing of somatosensory stimulus features and cognitive and motor processes related to the organization of appropriate behaviours (i.e. flight/fight responses, complex behavioural reflexes, changes of motivational responses and other fronto-cortical control manoeuvres). From our data, it appears that the somatosensory features of noxious stimuli are still evaluated properly during hypnotic analgesia, as they are in the non-hypnotic control condition, but the output of this processing is not com-municated appropriately to other brain areas that complete the evaluation of these stimuli as being painful and which are responsible for the organization of proper behaviours to

pain. Such a hypothesis can be tested by means of an analysis of the coupling between different brain areas. An adequate method is the analysis of coherences. We will report on such analyses in one of the following sections.

4.3.2 The role of hypnotic suggestibility on the effects of hypnotic analgesia and distraction of attention

In the previous section, it has been postulated that one of the possible reasons for the different results found for the effects of hypnotic analgesia and distraction on the percep-tion and feelings of pain might lie in the difference in hypnotic suggestibility. In a third study that used the same procedure as study 2 with 15 highly suggestible subjects and 15 subjects with a low level of susceptibility, these questions were addressed. In this study, 256 young healthy student volunteers were tested for hypnotic susceptibility using a German version of HGSHS: A and the German version of the SHSS: C. From this sample, 15 highly suggestible subjects and 15 subjects with a low degree of suggestibility with HGSHS scores or 9–12 (high) or 0–3 (low) and SHSS scores of either 9–12 (high) or 0–3 (low) participated in the experiment proper.

Results of the behavioural data demonstrated that pain intensity and pain aversiveness ratings were significantly reduced below the pain threshold for both groups of subjects when subjects were exposed to the distraction of attention as compared with the control condition. However, only highly suggestible subjects showed a reduction of pain ratings during hypnotic analgesia as compared with the control condition. In contrast, subjects with a low degree of suggestibility showed even a slight increase of pain ratings during hypnotic analgesia as compared with the control condition. LEP components were not different between groups.

Taken together, our recent studies and data from earlier investigations clearly demon-strate that hypnotic analgesia represents an effective demon-strategy for highly suggestible sub-jects to control acute experimentally induced pain. One hypothesis put forward to explain the effect as well as the observed changes in ERPs was that the effects of hypnotic analgesia are based on dissociation of neural activities of brain areas responsible for the analysis of somatosensory features of noxious stimuli and the final evaluation of these stimuli. Such a hypothesis can be tested by means of coherence analysis of neural activi-ties in different brain areas.

4.3.3 The breakdown in the communication between neural modules

That hypnotic analgesia might be based on a breakdown of neural communication between neural structures involved in the processing of pain was derived from recent studies on the effects of anaesthesia. A series of studies by Schwender and his group (Schwender et al. 1993, 1994, 1997; Daunderer and Schwender 2000) and suggestions by Kulli and Koch (1991) indicated that midlatency neural activity in response to auditory or visual stimulation became significantly smaller or completely suppressed as a function of the anaesthetic dose when subjects were treated by volatile anaesthetics or general anaesthetic agents as compared with placebo. Further analyses revealed that most of

these midlatency responses were characterized by fast oscillatory activities within the gamma band for which several research groups have postulated a putative role in consciousness (for hypnosis, see, for example, de Pascalis et al. 2004, de Pascalis, Chapter 5).

A recent study by our group further evaluated the putative role of gamma activity by inves-tigating the coherence of neural oscillations between different areas of the brain when subjects were exposed to hypnotic analgesia as compared with a control condition. While as in the studies of our group mentioned above, ERP amplitudes to painful stimuli applied to the tip of the middle finger were still unaffected during hypnotic analgesia and were of about a similar magnitude to during a non-hypnotic control condition, the results of an additional coherence analysis of brain activity indicated a significant decrease of coherence within the gamma band between somatosensory and frontal sites of the brain while subjects were hypnotized as compared with the control condition. This loss of coherence between somatosensory and frontal brain areas during hypnotic analgesia was hypothe-sized to reflect a similar breakdown of functional connectivity between the brain areas involved in the analysis of the somatosensory aspects of the noxious input and areas organ-izing the emotional and behavioural responses to pain as during states of anaesthesia.

Based on this study, we suggested that hypnosis affects integrative functions of the brain and induces an alteration or even a breakdown of communication between subunits within

Based on this study, we suggested that hypnosis affects integrative functions of the brain and induces an alteration or even a breakdown of communication between subunits within