Oliver H. G. Wilder-Smith

Subhypnotic Doses of Propofol Possess Direct Antiemetic Properties

Propofol is associated with a low incidence of postoperative nausea and vomiting. In a prospective, randomized, double-blind, placebo-controlled study, we investigated the possible direct antiemetic properties of a subhypnotic dose of propofol. Fifty-two ASA physical status I or II patients, aged 15–60 yr with nausea and vomiting after minor gynecologic, orthopedic, or digestive tract surgery, were included in the study and received either propofol (10 mg = 1 mL) or placebo (1 mL Intralipid) intravenously in the postanesthesia care unit. Patients treated with propofol experienced a larger reduction in nausea and vomiting than patients treated with placebo (81% vs 35% success rate; P < 0.05). Patients successfully treated had a similar incidence of relapse (propofol 28%; placebo 22%) within the first 30 min after therapy. Thirty-three percent of the propofol-treated patients and 44% of the placebo-treated patients showed a minor increase in sedation. The level of postoperative pain did not change in either group. Hemodynamic values remained unchanged in both groups. Pain on injection (7.6%) or dizziness (3.6%) only occurred in the propofol group. We conclude that propofol has significant direct antiemetic properties.

Recommendations on terminology and practice of psychophysical DNIC testing

a Department of Neurology, Rambam Health Care Campus, Technion Faculty of Medicine, Haifa, Israel b Department of Diagnostic Sciences, UMDNJ, Newark, NJ, USA c Laboratory of Experimental Pain Research, Aalborg University, Aalborg, Denmark d Hopital Ambroise Pare, Boulogne Billancourt, France e Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School Boston, MA, USA f College of Dentistry, University of Florida, Gainesville, FL, USA g Faculty of Health and Welfare Studies, University of Haifa, Haifa, Israel h Department of Molecular Medicine and Surgery, Karolinska Hospital/Institutet, Stockholm, Sweden i Department of Psychology, Bamberg University, Bamberg, Germany j Department of Surgery and Neurosurgery, Faculty of Medicine, Sherbrooke University, Sherbrooke, QC, Canada k Department of Anesthesiology, Radboud University, Nijmegen, Netherlands

Postoperative hyperalgesia: its clinical importance and relevance.

PAIN after surgery continues to be a major management challenge in clinical practice. In a recent meta-analysis covering some 20,000 patients and 800 publications, Dolin et al. concluded that 41% of all surgical patients still experience moderate to severe acute postoperative pain and that 24% experience inadequate pain relief. Unfortunately, acute postoperative pain control seems not to have substantially improved over the last decade or so. The picture is equally unsatisfactory regarding long-term outcomes, where chronic pain is increasingly identified as a direct consequence of surgical intervention. Recent surveys of chronic pain after surgery demonstrate that this problem is much more common than previously thought, with some types of surgery (e.g., thoracotomy, mastectomy, limb amputation) being associated with chronic pain incidences of more than 50% at 1 yr postoperatively. The past two decades have seen significant improvements in our understanding of the mechanisms underlying nociception and pain. A key insight has been that nervous system processing of nociception and pain is not hardwired, and that the gain of the nervous system can change as a result of noxious sensory inputs or the drugs used to modulate these. Nociception is now well accepted to result in sensitization of the nervous system, i.e., increased sensitivity regarding nociception and pain. Increased pain sensitivity is increasingly recognized as a potential—paradoxical and undesirable—effect of analgesic use to combat surgical pain and nociception, particularly for opioids. In a patient, such hyperexcitability of pain processing is expressed as increased pain for a given stimulus, a phenomenon termed hyperalgesia in the absence of modality shifts. The presence of hyperalgesia has a major impact on primary and secondary pain processing by the brain, with these changes having the potential to be both adaptive and maladaptive. These alterations may be detrimental in the early postoperative period for a number of reasons. First, hyperalgesia tends to increase the amount of pain the patient experiences—an unwanted outcome of itself—because of greater amplification of given noxious inputs. Second, more pain typically means more patient stress in the postoperative period, with the possibility of negative consequences for a variety of complications and outcomes. Finally, abnormal persistence of nervous system sensitization subsequent to nociception, i.e., excitatory neuroplasticity expressed as hyperalgesia and increased pain, is now considered a major candidate mechanism for the development of chronic pain. The reliable diagnosis of hyperalgesia is difficult based on clinical symptoms alone. The very definition of hyperalgesia—more pain accompanying a given stimulus— makes it clear that its detection is based on construction and comparison of stimulus–response curves before and after nociception or drug application. Therefore, the systematic diagnosis and quantification of hyperalgesia requires the formal, serial determination of stimulus dose–response curves under standardized conditions, a process termed quantitative sensory testing (QST). If postoperative hyperalgesia is not diagnosed, it will not be subject to targeted treatment, which fact may—as will be discussed below—be a contributing factor to the lack of substantive progress in postoperative analgesia mentioned above. The purpose of this review is, first, to explain how nociceptive and opioid-induced hyperalgesia may develop in the early postoperative period; second, to provide data indicating that such hyperalgesia can actually occur in clinical practice; third, to weigh the evidence to date supporting the usefulness of hyperalgesia management in the postoperative context; and fourth, to evaluate current knowledge regarding effective treatments of early postoperative hyperalgesia.

Only half of the chronic pain after thoracic surgery shows a neuropathic component.

UNLABELLED Chronic pain is a common complication after thoracic surgery. The cause of chronic post-thoracotomy pain is often suggested to be intercostal nerve damage. Thus chronic pain after thoracic surgery should have an important neuropathic component. The present study investigated the prevalence of the neuropathic component in chronic pain after thoracic surgery. Furthermore, we looked for predictive factors for prevalence and intensity of chronic pain. We contacted 243 patients who underwent a video-assisted thoracoscopy (VATS) or thoracotomy in the period between January 2004 and September 2006 by mail. Patients retrospectively received a questionnaire with the Dutch version of the PainDETECT Questionnaire, a validated screening tool for neuropathic pain. Results were analyzed from 204 patients (144 thoracotomies, 60 VATS). The prevalence of chronic pain was 40% after thoracotomy and 47% after VATS. Definite chronic neuropathic pain was present in 23% of the patients with chronic pain, with an additional 30% having probable neuropathic pain. Greater probability of neuropathic pain (ie, a higher total score of the PainDETECT) correlated with more intense chronic pain. Predictive factors for chronic pain were younger age (P = .01), radiotherapy (P = .043), pleurectomy (P = .04) and more extensive surgery (P < .001). PERSPECTIVE Up to half the chronic pain after thoracic surgery is not associated with a neuropathic component, which has not been reported to date. More extensive surgery and pleurectomy are predictive factors for chronic pain after thoracic surgery, suggesting a visceral component apart from nerve injury.

Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy.

Long-term potentiation (LTP) in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents.

Subhypnotic Doses of Propofol Relieve Pruritus Induced by Epidural and Intrathecal Morphine

We investigated the efficacy of subhypnotic doses of propofol for spinal morphine-induced pruritus in a prospective, randomized, double-blind, placebo-controlled study. Fifty patients, ASA physical status 1–3, with spinal morphine-induced pruritus were allocated to receive either 1 ml propofol (10 m

Descending Inhibitory Pain Modulation Is Impaired in Patients With Chronic Pancreatitis

BACKGROUND & AIMS Pain is a prominent symptom in chronic pancreatitis (CP), but the underlying mechanisms are incompletely understood. We investigated the role of descending pain modulation from supraspinal structures as well as central nervous system sensitization in patients with pain from CP. METHODS Twenty-five patients with CP and 15 healthy volunteers were included. Descending pain modulation was investigated by diffuse noxious inhibitory control (a descending inhibitory response after conditioning stimulation). Central pain processing was investigated as the perceptual responses to multimodal (electrical, thermal, and mechanical) stimulations of the rectosigmoid and evoked brain potentials after electrical stimulation of the rectosigmoid. RESULTS Compared with healthy volunteers, the efficacy of diffuse noxious inhibitory control was reduced in patients with CP (13% +/- 21% vs 39% +/- 22%, respectively; F = 3.8; P = .01); central sensitization was indicated by remote hyperalgesia in the rectosigmoid to electrical stimulation (21 +/- 15 mA vs 27 +/- 15 mA; F = 6.2; P = .02) and heat stimulation (51 degrees C +/- 5 degrees C vs 53 degrees C +/- 4 degrees C; F = 5.9; P = .02). Compared with controls, patients with CP had increased latency of the early P1 peak to rectosigmoid stimulation (85 +/- 21 ms vs 108 +/- 28 ms, respectively; P = .02), possibly reflecting reorganization of central pain pathways. CONCLUSIONS Patients with CP have impairments in inhibitory pain modulation and evidence of central sensitization. Treatment of their pain therefore should focus not only on the pancreas, but also on descending pain modulation from supraspinal structures and central nervous system sensitization.

Quantitative sensory testing and human surgery: effects of analgesic management on postoperative neuroplasticity.

Background Altered central nervous system sensory processing (neuroplasticity) is a basic mechanism underlying postoperative pain that can be made visible using quantitative sensory testing. Using quantitative sensory testing, the authors investigated how perioperative analgesia affects postoperative neuroplasticity and how this relates to clinical pain measures. Methods Patients undergoing back surgery received placebo, fentanyl, or ketorolac (n = 15 per group) before isoflurane-nitrous oxide anesthesia. Preoperatively to 5 days postoperatively, we measured thresholds to electrical skin stimulation at the incision site, arm, and leg; pain scores; and morphine patient-controlled analgesia consumption. Results Decreased pain thresholds versus preoperatively were seen 5 days postoperatively, with decreases greater for ketorolac (−63%;P = 0.00005 vs. preoperatively) than placebo (−45%;P = 0.008 vs. preoperatively) but nonsignificant for fentanyl (−36%;P = 0.9 vs. preoperatively). Mainly nonnociceptive thresholds were increased up to 24 h postoperatively. Postoperative clinical pain measures were similar across drug groups. Postoperative pain tolerance threshold changes did not correlate with preoperative clinical pain measures but were inversely related to preoperative thresholds for placebo and ketorolac but not fentanyl. Conclusions Without analgesia, neuroplasticity after surgery was inhibitory the first 24 h and followed at 5 days by excitation. Fentanyl efficiently preempted this hyperalgesia, but hyperalgesia was greater with ketorolac than with placebo. Clinical pain measures neither reflected the different effects of ketorolac and fentanyl on postoperative neuroplasticity nor permitted prediction of postoperative neuroplasticity. The information obtained by perioperative quantitative sensory testing is separate from and additional to that from clinical pain measures and may enable more mechanism-based approaches to surgical analgesia management in the future.

Preoperative back pain is associated with diverse manifestations of central neuroplasticity.

&NA; Increased or decreased gain in central nervous system processing after surgery, i.e. neuroplasticity, may play an important role in postoperative pain. Identification of patient subgroups particularly vulnerable to either type of post‐surgical neuroplasticity is thus of interest. Preoperative pain has also been suggested to increase vulnerability to post‐surgical chronic pain complications due to central facilitation. To study if back pain preoperatively is associated with differences in central sensory processing, we measured transcutaneous electric sensation, pain detection and pain tolerance thresholds at the upper arm, lower back and lower leg in 52 consecutive patients scheduled for back surgery in a blinded, prospective fashion. Patients with no pain had significantly lower pain thresholds than patients with pain in the leg, and significantly higher pain thresholds than those with pain in the back. These results suggest that preoperative pain can induce diverse central neuroplastic changes, i.e. inhibition and facilitation, and that the nature of this neuroplasticity depends on the nature of the pain involved. The presence of facilitation may be the basis of the increased vulnerability described in some studies of patients with significant preoperative pain, whereas the implications of reduced pain sensitivity are less clear. The demonstration of neuroplasticity and its diversity are, however, likely to be of significant clinical relevance.

Chronic pancreatitis patients show hyperalgesia of central origin: A pilot study

Background The pain of chronic pancreatitis remains challenging to manage, with treatment all too often being unsuccessful. A main reason for this is lacking understanding of underlying mechanisms of chronic pain in these patients.