Methods Twenty-four subjects were enrolled in this study. The magnitude of pain, axon reflex flare, and areas of pin-prick hyperalgesia and touch-evoked allodynia were assessed in two consecutive sessions; prior to, and 2 h after drug administration. This protocol was repeated after 1 week. Subjects were randomized to receive either paracetamol (2 g) or a placebo. Results In comparison to the placebo arm there were no significant effects of paracetamol on pain, hyperalgesia, allodynia, or axon reflex flare. Pain and flare responses were highly reproducible on the same day ( r = 0.77 and r = 0.79, respectively), and after 1 week ( r = 0.6 and r = 0.71, respectively). The correlation between areas of hyperalgesia and allodynia was, however, significantly improved when the protocol was repeated on the same day ( r = 0.8 and r = 0.75), as opposed to after a week ( r = 0.54 and r = 0.53). Discussion The electrical pain model is a well established method for the assessment of intravenously applied analgesics. In order to assess effects of orally applied drugs the model had to be modified: for the assessment of hyperalgesia and allodynia a protocol repeating the model within 1 day proved to have advantages over repetition after 1 week. Keywords Cross-over study design Pain Hyperalgesia Axon reflex Paracetamol 1 Introduction Central sensitization plays a key role in the development and maintenance of many chronic pain conditions [9,13,20] . A previous study established an electrical stimulation protocol as an experimental model to investigate central sensitization processes as well as acute pain in human beings [10] . A recent study, however, demonstrated a continuous decline of pain ratings and areas of hyperalgesia within one session of investigation. These findings were most likely due to the constant stimulation paradigm [11] . Repetition of the stimulation protocol in a 1-week-interval revealed a successive decline of hyperalgesia, whereas pain ratings remained at a constant level. This psycho-physical pattern was observed in two different models of acute pain and central sensitization [8,11] . The effects of intravenous analgesic drugs on experimentally evoked axon reflex flare, pain, and hyperalgesia have already been investigated using various electrical stimulation protocols [3,10,18] . Due to the fast onset of analgesia after intravenous application the drug, the effects could easily be tested in one session. Placebo sessions were usually performed at 1- or 2-week intervals. Such stimulation paradigm was not applicable to orally administered drugs. In the present study the stimulation protocol was modified to explore the efficacy of orally administered drugs. Two stimulation sessions were performed on 1 day at an interval of 4 h, and were repeated after a week. Thereby we aimed for a lower variation of pain and hyperalgesia. Koppert et al. could already demonstrate reduced hyperalgesia and allodynia following intravenous application of 1 g paracetamol on [12] . In the present study the effects of 2 g of orally administered paracetamol on pain, axon reflex flare, pin-prick hyperalgesia, and touch-evoked allodynia were investigated hypothesizing that the antihyperalgesic effect of oral paracetamol could be confirmed using the modified experimental protocol due to lower variability of hyperalgesia. 2 Methods 2.1 Subjects and study design The study was conducted at the University Hospital of Erlangen-Nuremberg. The study protocol was approved by the Ethics Committee of the University according to the Good Clinical Practice guidelines and the Declaration of Helsinki. Twenty-four healthy volunteers (12 males and 12 females) were recruited and introduced to the stimulation procedures described below. Each subject provided written informed consent prior to the participation in the study. The subjects underwent a routine medical and physical examination and were screened for drug abuse. Women were screened for pregnancy. A double-blind, placebo-controlled, cross-over design was utilised. Each subject received the electrical stimulation protocol on 2 different days, separated by 1 week. The previously described stimulation protocol [10] was performed twice on the same day, with the first session being in the morning and the following session 4 h later in the afternoon. The afternoon session was performed on the contra-lateral forearm ( Fig. 1 ). 2.2 Treatment and dose rationale Two hours prior to each afternoon session tablets containing either 2 g of paracetamol, or sucrose as placebo were swallowed with 150 ml still mineral water. In this experimental model it had been shown previously that 1 g of paracetamol administered intravenously attenuates hyperalgesia and allodynia [12] . After application of 2 g of paracetamol administered intravenously in healthy subjects the maximum plasma concentration lies between 235 and 521 mmol/l, which is far below the 1000 mmol/l threshold for potential hepatotoxity [16] . In the present study, therefore, 2 g of paracetamol was applied, instead of the recommended 1 g, in order to achieve better analgesia without jeopardising safety. 2.3 Study procedures As described previously [10] intradermally delivered constant current stimuli were used to induce an axon reflex flare, ongoing pain, pin-prick hyperalgesia and touch-evoked allodynia. Two intradermal electrodes (Dermal Dialysis, Erlangen, Germany) were inserted in the central volar forearm. Current pulses (pulse width 0.5 ms, 2 Hz) of alternating polarity were delivered via a constant current stimulator (DS7A mod, Digitimer, Hertforshire, United Kingdom). The current intensity was gradually increased targeting a pain rating of 5–6 on the 11-point numeric rating scale (NRS) with the endpoints 0 (no pain) and 10 (maximum pain imaginable). Current intensity was halted at this level for 2 min, during which the perceived pain gradually declined. After the 2-min stimulation period the estimated pain was documented. The current was then adjusted to gain a pain rating of 5–6 NRS again, kept constant for another 2 min, and followed by another pain rating of the subject. This procedure was repeated over 16 min, after which the current was kept constant for further 60 min. The stimulation pattern of consecutive current increase was recorded for each subject and was used in all subsequent sessions. 2.4 Psycho-physical assessment During the electrical stimulation protocol the subjects were asked to estimate the perceived intensity of ongoing pain on the NRS at 5-min intervals. The area of pin-prick hyperalgesia was measured at 20-min intervals using a hand-held von Frey filament, delivering a force of 450 mN. The borders of hyperalgesia were delineated by stimulating along four linear paths in radial orientation to the stimulation site (proximal vs. distal and lateral vs. medial). The measurements were started in an area of normal skin sensation and were continued in 0.5 cm steps towards the stimulation site. Subjects were instructed to report instantly any changes of sensation in terms of increased pain evoked by the filament. The area of touch-evoked allodynia was determined in 20-min intervals by gently stroking the skin surface with a hand-held cotton wool bud. The subjects were asked to report any new perception of pain or an unpleasant sensation. The areas of hyperalgesia and allodynia were indicated using a marker. The areas were calculated from the recorded distances, as described previously [2] . 2.5 Recording and analysis of the axon reflex flare Axon reflex vasodilatation was quantified by laser Doppler imaging (MoorLDI Ltd., Axminster, United Kingdom). A baseline image was recorded 20 min prior to the experimental protocol and at 20-min intervals after onset of the stimulation. Off- line analysis of skin blood flow was performed using dedicated software (MoorLDI Research Version 5.0, Axminster, United Kingdom), as described previously [5] . Mean flux and standard deviation were determined in a baseline image. Areas of axon reflex flare were determined as flux increase above the baseline scan exceeding 2 folds of the standard deviation. Flare area was assessed in each image of the sequence. 2.6 Statistical analysis All data were evaluated with Statistica7.1 software package (StatSoft, Tulsa, USA). Pain ratings, axon reflex flare, and areas of hyperalgesia and allodynia were calculated by analysis of variance (ANOVA). Variances of the mean ( s 2 ) between the sessions ( j 1 and j 2 ) were calculated as follows: s 2 ( j 1 , j 2 ) = i − sum[(AUC( i , j 1 ) − AUC( i , j 2 )) 2 ]/ n . Variances of the mean squares ( r 2 ) between the sessions were calculated as follows: r 2 ( j 1 , j 2 ) = s 2 ( j 1 , j 2 )/ s 2 (1,3), with AUC = area under curve; i = panelist-index; j = session-index; n = number of panelists (=24). p -Values less than 5% were considered as significant. All values were given as mean ± standard error of the mean (SEM). 3 Results 3.1 Gender variability and paracetamol effects There were no significant gender differences regarding flare development ( p = 0.26, ANOVA), pain ( p = 0.36), touch-evoked allodynia ( p = 0.30) or pin-prick hyperalgesia ( p = 0.91). Stimulation of the right or the left arm revealed no significant difference for flare ( p = 0.85, ANOVA), pain ( p = 0.22), allodynia ( p = 0.89) and hyperalgesia ( p = 0.80). A pre-treatment with paracetamol revealed no significant effect on flare ( p = 0.96), pain ( p = 0.7), allodynia ( p = 0.77), or pin-prick hyperalgesia ( p = 0.83) (data not shown). 3.2 Variability of axon reflex flare, pain, pin-prick hyperalgesia, and touch-evoked allodynia Pain ratings ( r = 0.86 and r = 0.68 for paracetamol and placebo, respectively), and axon reflex flare areas ( r = 0.72 and r = 0.87 for paracetamol and placebo, respectively) highly correlated between the two sessions performed on the same day within a 4-h interval ( Fig. 2 , left column). When pain ratings and flare areas were compared between the sessions repeated after 1 week there was a slightly higher variability for pain ratings ( r = 0.6) and axon reflex flare areas ( r = 0.71) ( Fig. 2 , right column). Similar to the results obtained for pain and axon reflex flare, areas of pin-prick hyperalgesia ( r = 0.86 and r = 0.75 for paracetamol and placebo, respectively) and touch-evoked allodynia ( r = 0.76 and r = 0.75 for paracetamol and placebo, respectively) were highly reproducible when electrical stimulation was repeated after 4 h ( Fig. 3 , left column). When electrical stimulation was repeated after 1 week there was still a significant correlation between the areas ( r = 0.54 and r = 0.53 for pin-prick hyperalgesia and touch-evoked allodynia, respectively). The correlation, however, was considerably less tight in comparison to the repetition of the test on the same day ( Fig. 3 , right column). There was no significant difference between pain ratings and areas of mechanical hypersensitivity when assessments were performed on the same day. When comparing pain and hyperalgesia induced in the morning sessions at a 1-week interval no significant differences for pain ( p = 0.44), hyperalgesia ( p = 0.11), and allodynia ( p = 0.82) were assessed, albeit there was a tendency to decline. Only the electrically induced flare area was slightly smaller when repeated at a 1-week interval (AUC session 1: 84.5 ± 21.9, AUC session 3: 71.0 ± 23.7, p = 0.045). In order to evaluate the differences in variability between different sessions, the variance for repetitions at 1-week interval was calculated ( Table 1 ). Variances for pain ratings, flare area and areas of mechanical hypersensitivity were lower when repetitions were performed on the same day. A particular reduction was observed for hyperalgesia that reached only 37–50% of the variation calculated for the 1-week interval. In contrast, variances of flare response were already pretty low for the 1-week interval and did only decrease to 57–80% when calculated for the repetition on the same day ( Table 1 ). 3.3 Adverse events All study treatments and procedures were tolerated well and no subject withdrew from the study. Each subject cooperated fully during the assessments. 4 Discussion The electrical stimulation used in the current study activates a subpopulation of mechano-insensitive C-nociceptors (silent nociceptors). This class of nociceptors is involved in the induction of axon reflex flare and secondary mechanical hyperalgesia [19] . The activation of the axons of the nociceptors using an electrical stimulation leads to a well controlled firing frequency of the nociceptors. The resulting action potentials are transmitted to the central synapses as well as to the peripheral terminals. At the peripheral terminals they induce the release of neuropetides, which in turn cause the development of an axon reflex flare. The assessment of this axon reflex flare is a valuable and an objective tool to test the activation of nociceptors. In addition to the peripheral effects, the central sensitization following continuous electrical stimulation can be assessed psycho-physically, measuring the development of hyperalgesia. Common analgesic drugs have shown to differential efficacy to attenuate electrically induced pain and hyperalgesia [2,10,17] . In addition to the development of secondary hyperalgesia around the stimulation electrodes, electrical stimulation or capsaicin injection also causes spreading mechanical hypesthesia [7] that can also be measured contra-laterally [4] and thus is assumed to be of central origin. In contrast to clinical pain, there is no evidence for contra-lateral spread of hyperalgesia in human pain models [4,7] . In the present study there was no significant effect of 2 g orally applied paracetamol on the magnitude of the estimated pain. This was in accordance with previous studies, in which pain thresholds to acute, noxious mechanical or thermal stimulation were not affected by this class of drugs [1,6,15] . Koppert et al. could demonstrate a significant attenuation of secondary hyperalgesia following intravenous administration of 1 g paracetamol [12] . This finding is of particular interest as it provides evidence for a spinal effect of paracetamol that is confined to a reduction of secondary mechanical hyperalgesia, but not to pain intensity. This pattern of antihyperalgesic effect has also been shown for gabapentin in the electrical human pain model [2,17] . In contrast to our expectations there was no significant reduction of hyperalgesia or allodynia after oral administration of 2 g paracetamol in the present study. The different result could be attributed to either pharmacokinetic differences or the experimental set up. Higher peak plasma concentrations upon intravenous injection might lead to higher central concentrations and hence more efficient antihyperalgesic activity. Higher central levels of paracetamol following intravenous injection as compared to oral application can be assumed regarding the higher occurrence of central side effects for the i.v. routes [14] . The onset of an analgesic effect can be expected by few minutes if paracetmol is applied intravenously [14] . An internal control without a drug infusion can therefore be easily performed within the same experimental session using the pre-injection baseline as a control level. This experimental set up can, however, not be easily used for the assessment of orally administered drugs for the following two reasons: (1) from an ethical point of view the duration of the experimental protocol may exceed the tolerance level of the recruited subjects; (2) a continuous stimulation leads to a gradual decline of the investigated parameters, in particular pain and hyperalgesia [11] . A similarly declining area of hyperalgesia was observed in the present study. This decline could be partly due to an endogenous opioid release, since in a previous work it could be shown that naloxone could prevent it [11] . In the present study, therefore, a cross-over design with two sessions on the same day, followed by two sessions a week later was chosen for the investigation of orally administered drugs. This experimental setting ensured an internal control between the sessions, revealed a high reproducibility of the analyzed parameters within 1 day, and, to a lesser extent, within 1 week. This study protocol could serve as an improved experimental setting for the analysis of the efficacy of analgesics on pain and hyperalgesia. 5 Conclusion A new experimental protocol of electrically induced pain and hyperalgesia was established to examine orally administered drugs. This experimental setting ensured an internal control between the sessions, revealed a high reproducibility of pain intensity and areas of mechanical hypersensitivity within 1 day and within 1 week. This study protocol could serve as an improved experimental setting for the analysis of the efficacy of analgesics on pain and hyperalgesia. Declaration of funding This study was funded by the Klinische Forschergruppe KFG 107 and the Kompetenzzentrum Schmerz , State Baden-Württemberg, Germany. Sponsoring preparation of the article has been provided by AstraZeneca , Sweden. Declaration of financial relationship There are no relationships to be declared. Conflict of interest None of the authors has any actual or potential conflict of interest concerning this work. Acknowledgement The authors gratefully acknowledge Niloufar Dusch for her editorial assistance. References [1] A. Bickel S. Dorfs M. Schmelz C. Forster W. Uhl H.O. Handwerker Effects of antihyperalgesic drugs on experimentally induced hyperalgesia in man Pain 76 1998 317 325 [2] B.A. Chizh M. Dusch M. Puthawala M. Schmelz L.M. Cookson R. Martina J. Brown W. Koppert The effect of intravenous infusion of adenosine on electrically evoked hyperalgesia in a healthy volunteer model of central sensitization Anesth Analg 99 2004 816 822 [table] [3] B.A. Chizh M. Gohring A. Troster G.K. Quartey M. Schmelz W. Koppert Effects of oral pregabalin and aprepitant on pain and central sensitization in the electrical hyperalgesia model in human volunteers Br J Anaesth 98 2007 246 254 [4] C.R. De C. Maihofner Centrally mediated sensory decline induced by differential C-fiber stimulation Pain 138 2008 556 564 [5] H. Eisenbarth R. Rukwied M. Petersen M. Schmelz Sensitization to bradykinin B1 and B2 receptor activation in UV-B irradiated human skin Pain 110 2004 197 204 [6] C. Forster W. Magerl A. Beck G. Geisslinger T. Gall K. Brune H.O. Handwerker Differential effects of dipyrone, ibuprofen, and paracetamol on experimentally induced pain in man Agents Actions 35 1992 112 121 [7] C. Geber W. Magerl R. Fondel M. Fechir R. Rolke T. Vogt R.D. Treede F. Birklein Numbness in clinical and experimental pain—a cross-sectional study exploring the mechanisms of reduced tactile function Pain 139 2008 73 81 [8] A. Hughes A. Macleod J. Growcott I. Thomas Assessment of the reproducibility of intradermal administration of capsaicin as a model for inducing human pain Pain 99 2002 323 331 [9] T.S. Jensen H. Gottrup S.H. Sindrup F.W. Bach The clinical picture of neuropathic pain Eur J Pharmacol 429 2001 1 11 [10] W. Koppert S.K. Dern R. Sittl S. Albrecht J. Schuttler M. Schmelz A new model of electrically evoked pain and hyperalgesia in human skin: the effects of intravenous alfentanil, S(+)-ketamine, and lidocaine Anesthesiology 95 2001 395 402 [11] W. Koppert J. Filitz A. Troster H. Ihmsen M. Angst H. Flor J. Schuttler M. Schmelz Activation of naloxone-sensitive and -insensitive inhibitory systems in a human pain model J Pain 6 2005 757 764 [12] W. Koppert A. Wehrfritz N. Korber R. Sittl S. Albrecht J. Schuttler M. Schmelz The cyclooxygenase isozyme inhibitors parecoxib and paracetamol reduce central hyperalgesia in humans Pain 108 2004 148 153 [13] M.J. Millan The induction of pain: an integrative review Prog Neurobiol 57 1999 1 164 [14] P.L. Moller S. Sindet-Pedersen C.T. Petersen G.I. Juhl A. Dillenschneider L.A. Skoglund Onset of acetaminophen analgesia: comparison of oral and intravenous routes after third molar surgery Br J Anaesth 94 2005 642 648 [15] K.L. Petersen J. Brennum J.B. Dahl Experimental evaluation of the analgesic effect of ibuprofen on primary and secondary hyperalgesia Pain 70 1997 167 174 [16] S.R. Rose Subtleties of managing acetaminophen poisoning Am J Hosp Pharm 51 1994 3065 3068 [17] M. Segerdahl Multiple dose gabapentin attenuates cutaneous pain and central sensitisation but not muscle pain in healthy volunteers Pain 125 2006 158 164 [18] A. Troster R. Sittl B. Singler M. Schmelz J. Schuttler W. Koppert Modulation of remifentanil-induced analgesia and postinfusion hyperalgesia by parecoxib in humans Anesthesiology 105 2006 1016 1023 [19] C. Weidner M. Schmelz R. Schmidt B. Hansson H.O. Handwerker H.E. Torebjork Functional attributes discriminating mechano-insensitive and mechano-responsive C nociceptors in human skin J Neurosci 19 1999 10184 10190 [20] C.J. Woolf G.J. Bennett M. Doherty R. Dubner B. Kidd M. Koltzenburg R. Lipton J.D. Loeser R. Payne E. Torebjork Towards a mechanism-based classification of pain? Pain 77 1998 227 229

Task: In a multi-tiered process, a new established working committee of the German Society of Anaesthesiology and Intensive Care Medicine (DGAI) was supposed to create a national catalogue of the leaning objectives in anaesthesiology, also to include subject-specific parts applicable to intensive care medicine, emergency and pain medicine. To this end, both contents and method had to undergo revision. Methods: A total of eight work steps were carried out. After establishing an overview in the shape of a mind map, the catalogues of learning objectives already existing at the German universities were reviewed and the mind map was supplemented accordingly. After deciding on an electronic tabular format, own learning-objective operationalisations and competence levels were defined. Individual learning objectives were then elaborated in the previously defined operationalisation semantics, in conformity with the mind-map template. Framework formulations, an introduction and the incorporation of recommendations for conveying and examining the contents finally completed the catalogue. Results: Altogether, a detailed volume with over 800 items was created which, after its adoption by the executive committee of the DGAI, was immediately made available to all university locations as a working tool. Indications given with regard to the conveyance and examination of the learning objectives were intended to support the development of curricular frameworks at the faculties. Outlook: Some faculties have implemented and already made experiences with the catalogue of learning objectives. First evaluations are forthcoming. The structure and some of the developmental steps of the catalogue of learning objectives may serve as an essential blueprint for the current elaboration of the new model statues for the further qualification for board-certified anaesthesiologists and the additional qualification in the field of emergency medicine.

Treatment of patients with multiple injuries has improved in recent years but still remains a major challenge for the treating team. The treatment in the emergency room represents the interface between prehospital and clinical trauma care. Management of patients with multiple injuries in the emergency room aims at a rapid diagnosis and treatment of life-threatening injuries. Adequate trauma care requires not only structural but also human resources. Recommendations are given by the Deutsche Gesellschaft fur Unfallchirurgie (DGU) for all hospitals. The cooperation of a well-rehearsed trauma team is necessary to guarantee optimal trauma care. Special training concepts [i.e. Advanced Trauma Life Support (ATLS)((R))] can help to establish treatment algorithms. An internal and external quality management can increase the efficiency of the treatment of patients with multiple injuries.

Wehrfritz, A. P.; Richebe, P.; Noel, N.; Apiou - Sbirlea, G.; Koppert, W. Author Information

European Journal of PainVolume 13, Issue S1 p. S124-S124 410 A RANDOMIZED PHASE I TRIAL EVALUATING THE ANTI-HYPERALGESIC AND ANALGESIC EFFECTS OF 50%–50% N2O—O2 A. Wehrfritz, A. Wehrfritz Department of Anaesthesiology, University hospital, Erlangen, GermanySearch for more papers by this authorP. Richebe, P. Richebe Department of Anesthesiology and Pain Medicine, University of Washington MC, Seattle, United StatesSearch for more papers by this authorN. Noel, N. Noel CRCD, Air Liquide, Jouy-en-Josas, FranceSearch for more papers by this authorG. Apiou-Sbirlea, G. Apiou-Sbirlea CRCD, Air Liquide, Jouy-en-Josas, FranceSearch for more papers by this authorW. Koppert, W. Koppert Department of Anaesthesiology, University hospital, Erlangen, GermanySearch for more papers by this author A. Wehrfritz, A. Wehrfritz Department of Anaesthesiology, University hospital, Erlangen, GermanySearch for more papers by this authorP. Richebe, P. Richebe Department of Anesthesiology and Pain Medicine, University of Washington MC, Seattle, United StatesSearch for more papers by this authorN. Noel, N. Noel CRCD, Air Liquide, Jouy-en-Josas, FranceSearch for more papers by this authorG. Apiou-Sbirlea, G. Apiou-Sbirlea CRCD, Air Liquide, Jouy-en-Josas, FranceSearch for more papers by this authorW. Koppert, W. Koppert Department of Anaesthesiology, University hospital, Erlangen, GermanySearch for more papers by this author First published: 12 January 2012 https://doi.org/10.1016/S1090-3801(09)60413-4Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume13, IssueS1September 2009Pages S124-S124 RelatedInformation

European Journal of PainVolume 13, Issue S1 p. S128-S128 425 TOPICAL LIDOCAINE IN A HUMAN PAIN MODEL REDUCES PAIN SENSATION AND QUANTITY OF EPIDERMAL NERVE FIBRES A. Wehrfritz, A. Wehrfritz Department of Anaesthesiology, University hospital, Erlangen, GermanySearch for more papers by this authorA. Leffler, A. Leffler Department of Anaesthesiology, University hospital, Erlangen, GermanySearch for more papers by this authorB. Namer, B. Namer Department of Anaesthesiology, University hospital, Erlangen, GermanySearch for more papers by this authorC. Müller, C. Müller Department of Anaesthesiology, University hospital, Erlangen, GermanySearch for more papers by this authorW. Koppert, W. Koppert Department of Anaesthesiology, University hospital, Erlangen, GermanySearch for more papers by this author A. Wehrfritz, A. Wehrfritz Department of Anaesthesiology, University hospital, Erlangen, GermanySearch for more papers by this authorA. Leffler, A. Leffler Department of Anaesthesiology, University hospital, Erlangen, GermanySearch for more papers by this authorB. Namer, B. Namer Department of Anaesthesiology, University hospital, Erlangen, GermanySearch for more papers by this authorC. Müller, C. Müller Department of Anaesthesiology, University hospital, Erlangen, GermanySearch for more papers by this authorW. Koppert, W. Koppert Department of Anaesthesiology, University hospital, Erlangen, GermanySearch for more papers by this author First published: 12 January 2012 https://doi.org/10.1016/S1090-3801(09)60428-6Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume13, IssueS1September 2009Pages S128-S128 RelatedInformation

European Journal of PainVolume 13, Issue S1 p. S20a-S20 43 Topical Seminar Summary: ALTERED SENSITIVITY TO OPIOID THERAPY: IS IT THE OPIOID, THE PAIN SYNDROME OR THE PATIENT THAT MATTERS? E. Eisenberg, E. Eisenberg Rambam Medical Center, The Technion — Israel Institute of Technology, Haifa, IsraelSearch for more papers by this authorW. Koppert, W. Koppert Medical School Hannover, Hannover, GermanySearch for more papers by this authorC. Maier, C. Maier Berufsgenossenschaftliches Universitaetsklinikum Bergmannsheil GmbH, Bochum, GermanySearch for more papers by this authorD. Pud, D. Pud Haifa University, Haifa, IsraelSearch for more papers by this author E. Eisenberg, E. Eisenberg Rambam Medical Center, The Technion — Israel Institute of Technology, Haifa, IsraelSearch for more papers by this authorW. Koppert, W. Koppert Medical School Hannover, Hannover, GermanySearch for more papers by this authorC. Maier, C. Maier Berufsgenossenschaftliches Universitaetsklinikum Bergmannsheil GmbH, Bochum, GermanySearch for more papers by this authorD. Pud, D. Pud Haifa University, Haifa, IsraelSearch for more papers by this author First published: 12 January 2012 https://doi.org/10.1016/S1090-3801(09)60046-XRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume13, IssueS1September 2009Pages S20a-S20 RelatedInformation

Background: Nerve injury and tissue inflammation can result in spontaneous and evoked pain (hyperalgesia). Basically, primary hyperalgesia is located in the area of injury and is a result of peripheral sensitization, whereas secondary mechanical hyperalgesia develops in the surrounding tissue due to mechanisms of central sensitization. Sodium channel blockade is known for reduction of spontaneous pain and hyperalgesia by predominantly central mechanisms. Therefore, the aim of the present study was to determine changes in cerebral processing of mechanical hyperalgesia induced by pharmacological modulation using lidocaine.

The purpose of this study was to investigate whether parasympathetic cholinergic pathways are involved in the regulation of orofacial blood flow. The effect of atropin (1 mg, iv.) on blood flow responses in the lower lip, nose and hand during painful tooth stimulation was studied in healthy human subjects (n=8). In all subjects, tooth stimulation caused a long lasting vasodilatation in the lower lip. During stimulation there was a transient elevation in heart rate (HR) and blood pressure (BP) concomitantly with a blood flow decrease in the finger and nose. With atropin, the pain-induced HR and BP elevations and blood flow reductions in the nose and finger were decreased. However, the pain-induced blood flow increase in the lip was not changed. This study indicates that the tooth stimulation-induced vasodilatation in the lip is not based on parasympathetic cholinergic mechanisms.