Noxious stimulation response index: a novel anesthetic state index based on hypnotic-opioid interaction

The noxious stimulation response index (NSRI) is a novel anesthetic depth index ranging between 100 and 0, computed from hypnotic and opioid effect-site concentrations using a hierarchical interaction model. The authors validated the NSRI on previously published data.

The role of central hypersensitivity in the determination of intradiscal mechanical hyperalgesia in discogenic pain

OBJECTIVE: The primary aim of the present study was to investigate whether there is a relationship between central hypersensitivity (assessed by pressure pain thresholds of uninjured tissues) and intradiscal pain threshold during discography. The secondary aim was to test the hypothesis that peripheral noxious stimulation dynamically modulates central hypersensitivity. PATIENTS: Twenty-four patients with positive provocation discography were tested for central hypersensitivity by pressure algometry before and after the intervention with assessments of pressure pain detection and tolerance thresholds. Intradiscal pain threshold was assessed by measuring intradiscal pressure at the moment of pain provocation during discography. Correlation analyses between intradiscal pain threshold and pressure algometry were made. For the secondary aim, pressure algometry data before and after discography were compared. RESULTS: Significant correlation with intradiscal pain threshold was found for pressure pain detection threshold at the toe (regression coefficient: 0.03, P = 0.05) and pressure pain tolerance thresholds at the nonpainful point at the back (0.02, P = 0.024). Tolerance threshold at the toe was a significant predictor for intradiscal pain threshold only in multiple linear regression (0.036, P = 0.027). Detection as well as tolerance thresholds significantly decreased after discography at the painful and the nonpainful point at the back, but not at the toe. CONCLUSIONS: Central hypersensitivity may influence intradiscal pain threshold, but with a modest quantitative impact. The diagnostic value of provocation discography is therefore not substantially impaired. Regional, but not generalized central hypersensitivity is dynamically modulated by ongoing peripheral nociceptive input.

Closed-loop control of mean arterial blood pressure during surgery with alfentanil: clinical evaluation of a novel model-based predictive controller

BACKGROUND: In contrast to hypnosis, there is no surrogate parameter for analgesia in anesthetized patients. Opioids are titrated to suppress blood pressure response to noxious stimulation. The authors evaluated a novel model predictive controller for closed-loop administration of alfentanil using mean arterial blood pressure and predicted plasma alfentanil concentration (Cp Alf) as input parameters. METHODS: The authors studied 13 healthy patients scheduled to undergo minor lumbar and cervical spine surgery. After induction with propofol, alfentanil, and mivacurium and tracheal intubation, isoflurane was titrated to maintain the Bispectral Index at 55 (+/- 5), and the alfentanil administration was switched from manual to closed-loop control. The controller adjusted the alfentanil infusion rate to maintain the mean arterial blood pressure near the set-point (70 mmHg) while minimizing the Cp Alf toward the set-point plasma alfentanil concentration (Cp Alfref) (100 ng/ml). RESULTS: Two patients were excluded because of loss of arterial pressure signal and protocol violation. The alfentanil infusion was closed-loop controlled for a mean (SD) of 98.9 (1.5)% of presurgery time and 95.5 (4.3)% of surgery time. The mean (SD) end-tidal isoflurane concentrations were 0.78 (0.1) and 0.86 (0.1) vol%, the Cp Alf values were 122 (35) and 181 (58) ng/ml, and the Bispectral Index values were 51 (9) and 52 (4) before surgery and during surgery, respectively. The mean (SD) absolute deviations of mean arterial blood pressure were 7.6 (2.6) and 10.0 (4.2) mmHg (P = 0.262), and the median performance error, median absolute performance error, and wobble were 4.2 (6.2) and 8.8 (9.4)% (P = 0.002), 7.9 (3.8) and 11.8 (6.3)% (P = 0.129), and 14.5 (8.4) and 5.7 (1.2)% (P = 0.002) before surgery and during surgery, respectively. A post hoc simulation showed that the Cp Alfref decreased the predicted Cp Alf compared with mean arterial blood pressure alone. CONCLUSION: The authors' controller has a similar set-point precision as previous hypnotic controllers and provides adequate alfentanil dosing during surgery. It may help to standardize opioid dosing in research and may be a further step toward a multiple input-multiple output controller.

Does acupuncture needling induce analgesic effects comparable to diffuse noxious inhibitory controls?

Diffuse noxious inhibitory control (DNIC) is described as one possible mechanism of acupuncture analgesia. This study investigated the analgesic effect of acupuncture without stimulation compared to nonpenetrating sham acupuncture (NPSA) and cold-pressor-induced DNIC. Forty-five subjects received each of the three interventions in a randomized order. The analgesic effect was measured using pressure algometry at the second toe before and after each of the interventions. Pressure pain detection threshold (PPDT) rose from 299 kPa (SD 112 kPa) to 364 kPa (SD 144), 353 kPa (SD 135), and 467 kPa (SD 168) after acupuncture, NPSA, and DNIC test, respectively. There was no statistically significant difference between acupuncture and NPSA at any time, but a significantly higher increase of PPDT in the DNIC test compared to acupuncture and NPSA. PPDT decreased after the DNIC test, whereas it remained stable after acupuncture and NPSA. Acupuncture needling at low pain stimulus intensity showed a small analgesic effect which did not significantly differ from placebo response and was significantly less than a DNIC-like effect of a painful noninvasive stimulus.

Determination of the minimum alveolar concentration of isoflurane in Shetland ponies using constant current or constant voltage electrical stimulation

OBJECTIVE: To determine the minimum alveolar concentration (MAC) of isoflurane in Shetland ponies using a sequence of three different supramaximal noxious stimulations at each tested concentration of isoflurane rather than a single stimulation. STUDY DESIGN: Prospective, experimental trial. ANIMALS: Seven 4-year-old, gelding Shetland ponies. METHODS: The MAC of isoflurane was determined for each pony. Three different modes of electrical stimulation were applied consecutively (2 minute intervals): two using constant voltage (90 V) on the gingiva via needle- (CVneedle) or surface-electrodes (CVsurface) and one using constant current (CC; 40 mA) via surface electrodes applied to the skin over the digital nerve. The ability to clearly interpret the responses as positive, the latency of the evoked responses and the inter-electrode resistance were recorded for each stimulus. RESULTS: Individual isoflurane MAC (%) values ranged from 0.60 to 1.17 with a mean (+/-SD) of 0.97 (+/-0.17). The responses were more clearly interpreted with CC, but did not reach statistical significance. The CVsurface mode produced responses with a longer delay. The CVneedle mode was accompanied by variable inter-electrode resistances resulting in uncontrolled stimulus intensity. At 0.9 MAC, the third stimulation induced more positive responses than the first stimulation, independent of the mode of stimulation used. CONCLUSIONS: The MAC of isoflurane in the Shetland ponies was lower than expected with considerable variability among individuals. Constant current surface electrode stimulations were the most repeatable. A summation over the sequence of three supramaximal stimulations was observed around 0.9 MAC. CLINICAL RELEVANCE: The possibility that Shetland ponies require less isoflurane than horses needs further investigation. Constant current surface-electrode stimulations were the most repeatable. Repetitive supramaximal stimuli may have evoked movements at isoflurane concentrations that provide immobility when single supramaximal stimulation was applied.

Wound stimulation by growth-arrested human keratinocytes and fibroblasts: HP802-247, a new-generation allogeneic tissue engineering product

HP802-247 is a new-generation, allogeneic tissue engineering product consisting of growth-arrested, human keratinocytes (K) and fibroblasts (F) delivered in a fibrin matrix by a spray device.

Test-retest reliability of the nociceptive withdrawal reflex and electrical pain thresholds after single and repeated stimulation in patients with chronic low back pain

Recent studies have shown that the nociceptive withdrawal reflex threshold (NWR-T) and the electrical pain threshold (EP-T) are reliable measures in pain-free populations. However, it is necessary to investigate the reliability of these measures in patients with chronic pain in order to translate these techniques from laboratory to clinic. The aims of this study were to determine the test-retest reliability of the NWR-T and EP-T after single and repeated (temporal summation) electrical stimulation in a group of patients with chronic low back pain, and to investigate the association between the NWR-T and the EP-T. To this end, 25 patients with chronic pain participated in three identical sessions, separated by 1 week in average, in which the NWR-T and the EP-T to single and repeated stimulation were measured. Test-retest reliability was assessed using intra-class correlation coefficient (ICC), coefficient of variation (CV), and Bland-Altman analysis. The association between the thresholds was assessed using the coefficient of determination (r (2)). The results showed good-to-excellent reliability for both NWR-T and EP-T in all cases, with average ICC values ranging 0.76-0.90 and average CV values ranging 12.0-17.7%. The association between thresholds was better after repeated stimulation than after single stimulation, with average r (2) values of 0.83 and 0.56, respectively. In conclusion, the NWR-T and the EP-T are reliable assessment tools for assessing the sensitivity of spinal nociceptive pathways in patients with chronic pain.

Improving chondrogenesis: potential and limitations of SOX9 gene transfer and mechanical stimulation for cartilage tissue engineering

Articular cartilage injuries and degeneration affect a large proportion of the population in developed countries world wide. Stem cells can be differentiated into chondrocytes by adding transforming growth factor-beta1 and dexamethasone to a pellet culture, which are unfeasible for tissue engineering purposes. We attempted to achieve stable chondrogenesis without any requirement for exogenous growth factors. Human mesenchymal stem cells were transduced with an adenoviral vector containing the SRY-related HMG-box gene 9 (SOX9), and were cultured in a three-dimensional (3D) hydrogel scaffold composite. As an additional treatment, mechanical stimulation was applied in a custom-made bioreactor. SOX9 increased the expression level of its known target genes, as well as its cofactors: the long form of SOX5 and SOX6. However, it was unable to increase the synthesis of sulfated glycosaminoglycans (GAGs). Mechanical stimulation slightly enhanced collagen type X and increased lubricin expression. The combination of SOX9 and mechanical load boosted GAG synthesis as shown by (35)S incorporation. GAG production rate corresponded well with the amount of (endogenous) transforming growth factor-beta1. Finally, cartilage oligomeric matrix protein expression was increased by both treatments. These findings provide insight into the mechanotransduction of mesenchymal stem cells and demonstrate the potential of a transcription factor in stem cell therapy.