Testing Central Sources of Hyperalgesia in Irritable Bowel Syndrome Placebo and Nocebo Effects

The study just discussed was conducted as a standard clinical trial where patients were given an informed consent form, which stated that they "may receive an active pain reducing medication or an inert placebo agent'' (52). In this study, there was a significant pain-relieving effect of rectal lidocaine as compared to rectal placebo (p < 0.001), and there was a significant pain-relieving effect of rectal placebo as compared to the natural history condition (Fig. 4, left panel). Taking into consideration previous meta-analyses showing enhanced placebo effects in experimental studies compared to clinical trials (63), a second study was carried out, which was almost identical to the first study. The one difference was that in the second study the patients

Figure 4 (Left pane): Visual analog scale pain intensity ratings during rectal distension (35 mmHg). Three separate trials were performed: natural history, rectal placebo, and rectal lidocaine. This study was conducted with a standard clinical trial design, without suggestions for analgesia. Values are represented as mean ± SD, n = 10 IBS patients. (Right pane) Results of a second study wherein a verbal suggestion for analgesia was added. Note that unlike the first study, the placebo effect was large as that of lidocaine. Source: From Ref. 62.

Figure 4 (Left pane): Visual analog scale pain intensity ratings during rectal distension (35 mmHg). Three separate trials were performed: natural history, rectal placebo, and rectal lidocaine. This study was conducted with a standard clinical trial design, without suggestions for analgesia. Values are represented as mean ± SD, n = 10 IBS patients. (Right pane) Results of a second study wherein a verbal suggestion for analgesia was added. Note that unlike the first study, the placebo effect was large as that of lidocaine. Source: From Ref. 62.

were told "the agent you have just been given is known to significantly reduce pain in some patients'' at the onset of each treatment condition (rectal placebo and rectal lidocaine) (62). As shown in Figure 4 (right panel), a much larger placebo analgesic effect was found in the second study and the magnitude of placebo analgesia was so high (an effect size 2.0, Cohen's d) that there was no longer a significant difference between the magnitude of rectal lidocaine and rectal placebo. Hence, these two studies indicate that by adding an overt suggestion for pain relief, it is possible to increase the magnitude of placebo analgesia to a level that matches that of an active agent. It is important to recognize that these effects reflect antihyperalgesic effects, because both rectal lidocaine and placebo suggestions normalize the primary and secondary hyperalgesia and do not eliminate all pain from balloon distension. In fact, pain ratings of IBS patients after placebo or lidocaine are like those of normal control subjects (51,52,64).

Although lidocaine jelly potently reduced experimentally evoked pain in IBS patients for at least 50 minutes (52); one can question whether rectal application of lidocaine jelly can directly reduce ongoing abdominal pain in these patients, especially if the area of gastrointestinal abnormality includes the colon. Thus, a double-blind, crossover trial on 10 IBS patients was conducted to determine whether administration of intrarectal (300 mg) lidocaine in jelly form could ameliorate the ongoing abdominal pain associated with IBS (65). All of the patients that participated had intermittent left lower quadrant pain and diarrhea. Each patient participated in two sessions in which saline jelly (placebo) and lidocaine jelly were administered on a double-blind, crossover basis. Patients participated in these sessions at a time when their ongoing pain was at least three on a 0 to 10 VAS. In comparison to placebo saline jelly, lido-caine jelly significantly decreased abdominal pain for at least four hours, as shown in Figure 5. These results are understandable if the rectum is a major source of tonic afferent input that sustains widespread visceral hyperalgesia, similar to the critical foci that sustain widespread hyperalgesia/allodynia in CRPS patients (21).

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Everything You Need To Know About Baby Sleeping. Your baby is going to be sleeping a lot. During the first few months, your baby will sleep for most of theday. You may not get any real interaction, or reactions other than sleep and crying.

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