Ping-Heng Tan

Single-injection femoral nerve block lacks preemptive effect on postoperative pain and morphine consumption in total knee arthroplasty

OBJECTIVE Postoperative pain is severe after total knee arthroplasty (TKA). Therefore, femoral nerve block (FNB) is commonly used as an adjuvant to spinal anesthesia for TKA. Some anesthesia providers perform this preoperatively, while others perform it postoperatively. To our knowledge, no study has compared the relative benefits of the timing of performing the procedure. In this study, we investigated whether preoperative FNB would provide better analgesic effects than postoperative FNB in patients undergoing unilateral TKA. METHODS In this double-blind, randomized, controlled trial, we divided 82 patients (ASA physical status I-III) undergoing unilateral TKA into four groups: (1) a pre-treatment group, in which FNB was performed with 0.4 mL/kg 0.375% bupivacaine plus 1:200,000 epinephrine after spinal anesthesia but before the operation; (2) a post-treatment group, in which FNB was performed with the same drugs at similar dosages immediately after the operation; (3) a pre-control group, in which FNB was performed with normal saline in the same volume as the tested drugs before the operation; and (4) a post-control group, in which FNB was performed with normal saline in the same volume as the tested drug after the operation. At 2, 4, 6, 24, 48 and 72 postoperative hours, we recorded cumulative morphine consumption, visual analog pain scales (VAS), the time of first request for morphine and its side effects. We also measured knee maximum flexion range of motion once a day for 3 days. Our primary aim was to obtain cumulative morphine consumption in 24 hours. RESULTS Within the postoperative 24 hours, we found significant differences in cumulative morphine consumption between patients who received true FNB and those who did not (at 24 hours, treatment groups = 45.6 ± 31.7 and 33.5 ± 20.6 mg vs. controls = 70.8 ± 31.2 and 78.8 ± 37.7 mg, p < 0.001). We also found significant differences in VAS (at 24 hours, p < 0.001) and time to first request of morphine (p = 0.005) between the treatment group and the sham group. However, there were no significant differences in these values between the pre-surgical treatment group and the post-surgical treatment group. Beyond 24 hours, there were no significant differences in morphine consumption or maximum flexion range on day 2 and day 3 among the four groups. CONCLUSION Patients who received FNB used for total knee arthroplasty consumed significantly less postoperative morphine and had significant relief of post-TKA pain on postoperative day 1 than those who did not have FNB. However, at follow-up we found no significant differences in these values between those receiving FNB before surgery and those receiving it after surgery.

MicroRNA-based therapy in pain medicine: Current progress and future prospects

MicroRNAs (miRNAs) are small noncoding RNA molecules of 18-25 nucleotides in length that regulate gene expression involved in fundamental cell processes. The induction and chronification of pain is associated with many expressional changes in pain-related proteins. miRNA has the potential to regulate gene and protein expression associated with the induction and chronification of pain. Thus, miRNAs might have promise in therapy and as a diagnostic and prognostic biomarker in pain medicine. The application of miRNA has been an emerging field in pain research in recent years. Many studies focusing on the regulation of miRNAs under different tissue and nociceptive stimuli have been performed in recent years. In this review, we intend to introduce the most recent research in the field of miRNA related with pain medicine such as the expression and function of miRNA in different animal pain model, the challenge of application and delivery of miRNA in vivo, the potential toxic effects of miRNA and future problems in clinical application that need to be resolved. This review focuses on the results of miRNA in animal studies and the prospect for future success.

The effect of transoesophageal echocardiography probe insertion on tracheal cuff pressure

Increased tracheal cuff pressure during mechanical ventilation is associated with reduced mucosal blood flow and ischaemia, as well as postoperative sore throat. We assessed the potential effects of transoesophageal echocardiography probe insertion on the tracheal cuff pressure in patients undergoing cardiac surgery. Using a manometer, the cuff pressure of a high‐volume, low‐pressure tracheal tube (inner diameter 7.0 mm for women and 7.5 mm for men) was adjusted to 25–30 cmH2O before blind insertion of a transoesophageal echocardiography probe. The pressure changes were then recorded for 1 min. After probe insertion, the mean (SD) intra‐cuff pressure increased from 27.7 (1.5) to 36.2 (6.4) cmH2O (p < 0.001) and was > 35 cmH20 in 17/38 patients (45%). Our results suggest that transoesophageal echocardiography probe insertion may increase the tracheal cuff pressure more than that is generally recommended and therefore the latter should be routinely monitored under such circumstances.

RNA interference-mediated gene silence of the NR1 subunit of the NMDA receptor by subcutaneous injection of vector-encoding short hairpin RNA reduces formalin-induced nociception in the rat

&NA; There is accumulating evidence to implicate the importance of N‐methyl‐d‐aspartate (NMDA) receptors to the induction and maintenance of central sensitization during pain states. However, the use of NMDA receptor antagonists can often be limited by serious central nervous system side effects. The development of peripheral NMDA receptor antagonists that do not interfere with central glutamate processing can avoid adverse effects of the central nervous system. RNA interference is an evolutionarily conserved mechanism for silencing gene expression in which a targeted mRNA is degraded by a double‐stranded RNA sequence known as a small interfering RNA (siRNA). siRNAs can be derived from short hairpin (sh) RNAs, which can be expressed from plasmids or viral vectors to achieve long‐term gene silencing. In this study, we examined the effect of gene silence and antinociception on formalin‐induced pain by subcutaneous injection of vector‐encoding shRNA targeting the NR1 subunit of the NMDA receptor. The results revealed that subcutaneous injection of vector‐expressing NR1 shRNA could effectively diminish the nociception induced by formalin stimuli and inhibit gene expression of NR1 evidenced by a decreased level of mRNA and protein. The effect of antinociception and inhibition of NR1 expression by NR1 shRNA persisted for about 14 days. The data suggest that NR1 shRNA has therapeutic potential to provide long‐term treatment of pathological pain that is induced or maintained by peripheral nociceptor activity. Subcutaneous injection of NR1 short hairpin RNA has the therapeutic potential of providing long‐term treatment of pathological pain that is induced or maintained by peripheral nociceptor activity.

The pre-emptive analgesic effect of a cyclooxygenase-2 inhibitor in a rat model of acute postoperative pain

We examined the pre‐emptive analgesic effect of a cyclooxygenase (COX)‐2 inhibitor in a rat surgical pain model and characterised the changes in cutaneous COX‐2 around a surgical site. Thermal hyperalgesia and mechanical allodynia were tested in the rats for three days after incision and skin tissues were collected for analysis of COX‐2. There was decreased expression of cutaneous COX‐2 one day after surgical incision. Pre‐incision injection of the COX‐2 inhibitor significantly inhibited expression of COX‐2 and also reduced thermal hyperalgesia (but not mechanical allodynia) compared with the post‐incision COX‐2‐inhibitor injection group, one day after incision.

Lentiviral vector‐encoded microRNA‐based shRNA‐mediated gene knockdown of N‐methyl‐D‐aspartate receptors in skin reduces pain

RNA polymerase II promoters that drive the expression of rationally designed primary microRNA‐based shRNA, for example, shRNAmir, can produce more potent gene knockdown than RNA polymerase III promoters. Antagonists of peripheral N methyl‐D‐aspartate (NMDA) receptors that do not interfere with central glutamate processing would prevent the development of adverse central nervous system effects. Thus, in this study, we examined the effects of gene silencing and antinociception on formalin‐ and Complete Freunds adjuvant (CFA)‐induced pain in rats by subcutaneously injecting a lentiviral vector encoding a shRNAmir that targets the NR1 subunit of the NMDA receptor.

The antinociceptive effect of light-emitting diode irradiation on incised wounds is correlated with changes in cyclooxygenase 2 activity, prostaglandin e2, and proinflammatory cytokines

Background. Light-emitting diode (LED) phototherapy has been reported to relieve pain and enhance tissue repair through several mechanisms. However, the analgesic effect of LED on incised wounds has never been examined. Objectives. We examined the analgesic effect of LED therapy on incision pain and the changes in cyclooxygenase 2 (COX-2), prostaglandin E2 (PGE2), and the proinflammatory cytokines interleukin 6 (IL-6), IL-1β, and tumor necrosis factor α (TNF-α). Methods. Rats received LED therapy on incised skin 6 days before incision (L-I group) or 6 days after incision (I-L group) or from 3 days before incision to 3 days after incision (L-I-L group). Behavioral tests and analysis of skin tissue were performed after LED therapy. Results. LED therapy attenuated the decrease in thermal withdrawal latency in all the irradiated groups and the decrease in the mechanical withdrawal threshold in the L-I group only. The expression levels of COX-2, PGE2, and IL-6 were significantly decreased in the three LED-treated groups, whereas IL-1β and TNF-α were significantly decreased only in the L-I group compared with their levels in the I groups (p < 0.05). Conclusions. LED therapy provides an analgesic effect and modifies the expression of COX-2, PGE2, and proinflammatory cytokines in incised skin.

Integrated analysis of microRNA and mRNA expression profiles in the rat spinal cord under inflammatory pain conditions

Recent studies using microarray‐based approaches have demonstrated that microRNAs (miRNAs) are involved in pain processing pathways. However, a significant proportion of computational predictions of miRNA targets are false‐positive interactions. To increase the chance of identifying biologically relevant targets, we performed an integrated analysis of both miRNA and mRNA expression profiles in the rat spinal cord during complete Freunds adjuvant (CFA)‐induced inflammatory pain. We generated miRNA and mRNA arrays from the same corresponding samples on days 5 and 14 after CFA injection. Five miRNAs and 1096 mRNAs in the CFA 5d group and 16 miRNAs and 647 mRNAs in the CFA 14d group were differentially expressed based on a filter of at least a 1.5‐fold change in either direction. An integrated analysis revealed 54 mRNA targets with an inverse correlation to the expression patterns of three miRNAs in the CFA 5d group. Seventy‐five targets were inversely correlated to six miRNAs in the CFA 14d group. The miRNA–mRNA interaction networks revealed significant changes in miR‐124, miR‐149, miR‐3584 and their target genes, IL‐6R, ADAM19, LAMC1 and CERS2, in the CFA 5d group. In the CFA 14d group, significant changes were noted in miR‐124, miR‐29, miR‐34, miR‐30, miR‐338 and their target genes, TIMP2, CREB5 and EFNB1. We also investigated an interaction pair, miR‐124‐3p and IL‐6R, and the results showed that miR‐124‐3p could attenuate inflammatory pain and decrease IL‐6R expression in the spinal cord. These specific miRNAs and their target genes provide possible avenues for the diagnosis and treatment of inflammatory pain.

Difficult fiber-optic intubation in a patient with giant neck masses: The role of McCoy laryngoscope in elevating compressed laryngeal aperture

Airway management in patients with giant neck masses is usually a challenge to anesthesiologists. A giant neck mass could compress the airway and thus impede endotracheal intubation. We encountered a situation where the giant neck masses of a patient pushed the epiglottis posteriorly toward the posterior pharyngeal wall and compressed the laryngeal aperture narrowing after anesthetic induction, causing direct laryngoscopic intubation and sequential fiber-optic intubation failed. The neck masses twisted the aryepiglottic fold tortuously and clogged the laryngeal aperture tightly, making a flexible fiber-optic bronchoscope unable to pass through the laryngeal aperture. Later, we utilized a McCoy laryngoscope alternately to lift the compressed larynx up and away from the posterior pharyngeal wall, creating a passage and completing endotracheal intubation successfully with the aid of a gum elastic bougie. Our case suggested that the tilting tip blade of the McCoy laryngoscope could lever the tongue base up against the tumor mass compression to improve laryngeal views and facilitate endotracheal intubation when a difficult fiber-optic intubation was encountered on a compressed laryngeal aperture.

The N-methyl-D-aspartate (NMDA) receptor in skin, dorsal root ganglion and spinal cord: an ideal target gene for RNA interference therapy for pain relief

The NMDA receptor plays an important role in induction of pain hyperalgesia and allodynia by tissue trauma. Although the analgesic effect of NMDA receptor antagonists has been well reported in various experimental study and clinical pain trial, serious side effects were reported and limited their use in clinical medication. To obtain NMDA receptor antagonist with less side effects, an alternative approach is to use subtype-selective NMDA receptor antagonists. However, the effects of current available NMDA receptor antagonist’s drug are not absolute specific for antagonizing specific NMDA receptor subtypes.