Lack of Beneficial Effect for Preemptive Analgesia in Postoperative Pain Control

Cao

et al. 2015

The Journal of Pain

Self Cite

Chronic sleep disturbance-induced stress is known to increase basal pain sensitivity. However, most surgical patients frequently report short-term sleep disturbance/deprivation during pre- and post-operation periods and have normal pain perception pre-surgery. Whether this short-term sleep disturbance affects postsurgical pain is elusive. We here reported that pre- or post-exposure to rapid eye movement sleep disturbance (REMSD) 6 h daily for 3 consecutive days did not alter basal responses to mechanical, heat, and cold stimuli, but did delay recovery in incision-induced reductions in paw withdrawal threshold to mechanical stimulation and paw withdrawal latencies to heat and cold stimuli on the ipsilateral side of male or female rats. This short-term REMSD led to stress evidenced by an increase in swim immobility time, a decrease in sucrose consumption, and an elevation in the level of corticosterone in serum. Blocking this stress via intrathecal RU38486 or bilateral adrenalectomy abolished REMSD-caused delay in recovery of incision-induced reductions in behavioral responses to mechanical, heat, and cold stimuli. Moreover, this short-term REMSD produced significant reductions in the levels of mu opioid receptor and kappa opioid receptor, but not Kv1.2, in the ipsilateral L4/5 spinal cord and dorsal root ganglia on day 9 post-incision (but not post-sham surgery).

Section: Resultssupporting

confidence: 92%

Short-Term Sleep Disturbance–Induced Stress Does not Affect Basal Pain Perception, but Does Delay Postsurgical Pain Recovery

Cao

et al. 2015

The Journal of Pain

Self Cite

“…Despite the utilization of a variety of regional and neuroaxial analgesic techniques before surgery, post-operative pain remains a major stumbling block even when a variety of analgesics-opioids, local anesthetics and non-steroidal anti-inflammatory medications are used [38]. Along those lines, previously published animal work suggests that pre-incisional administration of the analgesic ketamine, a potent antagonist of the NMDA subtype of glutamate receptors results in pain relief that is not more effective or longer lasting than when ketamine is administered post-incisionally thus questioning the benefits of a pre-emptive pain management approach [39]. Our work with morphine when compared to ECN and Alphaxalone we present herein suggests that the common notion regarding the effectiveness of currently available preemptive modalities is most likely related to the cellular target that is being modulated.…”

Section: Discussionmentioning

confidence: 99%

Preemptive Analgesic Effect of Intrathecal Applications of Neuroactive Steroids in a Rodent Model of Post-Surgical Pain: Evidence for the Role of T-Type Calcium Channels

Tat

Joksimović

Krishnan

et al. 2020

Cells

Preemptive management of post-incisional pain remains challenging. Here, we examined the role of preemptive use of neuroactive steroids with activity on low-voltage activated T-type Ca2+ channels (T-channels) and γ-aminobutyric acid A (GABAA) receptors in the development and maintenance of post-incisional pain. We use neuroactive steroids with distinct effects on GABAA receptors and/or T-channels: Alphaxalone (combined GABAergic agent and T-channel inhibitor), ECN (T-channel inhibitor), CDNC24 (GABAergic agent), and compared them with an established analgesic, morphine (an opioid agonist without known effect on either T-channels or GABAA receptors). Adult female rats sustained the skin and muscle incision on the plantar surface of the right paw. We injected the agents of choice intrathecally either before or after the development of post-incisional pain. The pain development was monitored by studying mechanical hypersensitivity. Alphaxalone and ECN, but not morphine, are effective in alleviating mechanical hyperalgesia when administered preemptively whereas morphine provides dose-dependent pain relief only when administered once the pain had developed. CDNC24 on the other hand did not offer any analgesic benefit. Neuroactive steroids that inhibit T-currents—Alphaxalone and ECN—unlike morphine, are effective preemptive analgesics that may offer a promising therapeutic approach to the treatment of post-incisional pain, especially mechanical hypersensitivity.

Korean J Physiol Pharmacol

“…Thoracic extradural block with bupivacaine does not produce an early preemptive effect following thoracotomy [ 35 ]. In an animal model, preincisional treatment is not more beneficial than postincisional treatment for postoperative pain relief [ 36 ]. The lack of effects of preemptive analgesia in these cases may be caused by central sensitization which is responsible for the secondary development of pain, including neuronal plasticity [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Preemptive application of QX-314 attenuates trigeminal neuropathic mechanical allodynia in rats

Yoon

Son

Kim

et al. 2018

The aim of the present study was to examine the effects of preemptive analgesia on the development of trigeminal neuropathic pain. For this purpose, mechanical allodynia was evaluated in male Sprague-Dawley rats using chronic constriction injury of the infraorbital nerve (CCI-ION) and perineural application of 2% QX-314 to the infraorbital nerve. CCI-ION produced severe mechanical allodynia, which was maintained until postoperative day (POD) 30. An immediate single application of 2% QX-314 to the infraorbital nerve following CCI-ION significantly reduced neuropathic mechanical allodynia. Immediate double application of QX-314 produced a greater attenuation of mechanical allodynia than a single application of QX-314. Immediate double application of 2% QX-314 reduced the CCI-ION-induced upregulation of GFAP and p-p38 expression in the trigeminal ganglion. The upregulated p-p38 expression was co-localized with NeuN, a neuronal cell marker. We also investigated the role of voltage-gated sodium channels (Navs) in the antinociception produced by preemptive application of QX-314 through analysis of the changes in Nav expression in the trigeminal ganglion following CCI-ION. Preemptive application of QX-314 significantly reduced the upregulation of Nav1.3, 1.7, and 1.9 produced by CCI-ION. These results suggest that long-lasting blockade of the transmission of pain signaling inhibits the development of neuropathic pain through the regulation of Nav isoform expression in the trigeminal ganglion. Importantly, these results provide a potential preemptive therapeutic strategy for the treatment of neuropathic pain after nerve injury.