Loss of endogenous analgesia leads to delayed recovery from incisional pain in a rat model of chronic neuropathic pain

Ohta, Jo; Suto, Takashi; Kato, Daiki; Hiroki, Tadanao; Obata, Hideaki; Saito, Shigeru

doi:10.1016/j.brainres.2019.146568

Cited by 9 publications

(5 citation statements)

References 37 publications

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“…5 F) also suggested that spinal noradrenergic analgesia does not work in SHR during recovery after surgery (POD28). Some previous studies reported that chronic neuropathic pain impairs descending noradrenergic inhibition and produces pain chronification of additional acute pain 29 , 48 . Our present study suggests the existence of a population with impaired endogenous analgesia even without persistent pain, and that the group has a risk factor for prolonged pain after surgery.…”

Section: Discussionmentioning

confidence: 99%

“…We performed a power analysis for the primary outcome (NSIA) to determine the appropriate sample size. The analysis assumed a mean difference of 50 g in the withdrawal threshold in the left hind paw and a standard deviation of 30 g in each group according to the results of a previous study 48 . We determined that the use of more than 7 rats in each group would result in the detection of significant differences with 80% power at a significant level of α = 0.05.…”

Section: Methodsmentioning

confidence: 99%

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Rat model of attention-deficit hyperactivity disorder exhibits delayed recovery from acute incisional pain due to impaired descending noradrenergic inhibition

Suto

Kato

Koibuchi

et al. 2023

Sci Rep

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Chronic pain and attention-deficit hyperactivity disorder (ADHD) frequently coexist. However, the common pathology is still unclear. Attenuated noradrenergic endogenous analgesia can produce acute pain chronification, and dysfunction of noradrenergic systems in the nervous system is relevant to ADHD symptoms. Noxious stimuli-induced analgesia (NSIA) is measured to estimate noradrenergic endogenous analgesia in spontaneously hypertensive rats (SHR) as an ADHD model and control. Recovery of pain-related behaviors after paw incision was assessed. Contributions of noradrenergic systems were examined by in vivo microdialysis and immunohistochemistry. The SHR showed attenuated NSIA and needed a more extended period for recovery from acute pain. These results suggest ADHD patients exhibit acute pain chronification due to pre-existing attenuated noradrenergic endogenous analgesia. Immunohistochemistry suggests abnormal noradrenaline turnover and downregulation of the target receptor (alpha2a adrenoceptor). Standard ADHD treatment with atomoxetine restored NSIA and shortened the duration of hypersensitivity after the surgery in the SHR. NSIA protocol activated the locus coeruleus, the origin of spinal noradrenaline, of both strains, but only the control exhibited an increase in spinal noradrenaline. This result suggests dysfunction in the noradrenaline-releasing process and can be recognized as a novel mechanism of attenuation of noradrenergic endogenous analgesia.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Rat model of attention-deficit hyperactivity disorder exhibits delayed recovery from acute incisional pain due to impaired descending noradrenergic inhibition

Suto

Kato

Koibuchi

et al. 2023

Sci Rep

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“…An important question concerns the relationship between latent nociceptor hyperactivity and affective pain. Incision studies in rats consistently report that hypersensitivity to weak tactile stimulation and/or hypersensitivity to radiant heat (both utilizing paw withdrawal reflexes) persist for ~4-10 days and only occur in the injured hind paw 2,15,35,55,63,71,82,86 , although additional responses to stimulation of the hypersensitive hind paw may be expressed in other parts of the body 16,24 . We chose to examine two behaviors considered better indicators of affective pain than reflexive tests.…”

Section: Bilateral Extended Plantar Incision Reveals Mechanical Hyper...mentioning

confidence: 99%

Widespread latent hyperactivity of nociceptors outlasts enhanced avoidance behavior following incision injury

Bavencoffe,

Lopez,

Johnson

et al. 2024

Preprint

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Nociceptors with somata in dorsal root ganglia (DRGs) exhibit an unusual readiness to switch from an electrically silent state to a hyperactive state of tonic, nonaccommodating, low-frequency, irregular discharge of action potentials (APs). Ongoing activity (OA) during this state is present in vivo in rats months after spinal cord injury (SCI), and has been causally linked to SCI pain. OA induced by various neuropathic conditions in rats, mice, and humans is retained in nociceptor somata after dissociation and culturing, providing a powerful tool for investigating its mechanisms and functions. An important question is whether similar nociceptor OA is induced by painful conditions other than neuropathy. The present study shows that probable nociceptors dissociated from DRGs of rats subjected to postsurgical pain (induced by plantar incision) exhibit OA. The OA was most apparent when the soma was artificially depolarized to a level within the normal range of membrane potentials where large, transient depolarizing spontaneous fluctuations (DSFs) can approach AP threshold. This latent hyperactivity persisted for at least 3 weeks, whereas behavioral indicators of affective pain (hindpaw guarding and increased avoidance of a noxious substrate in an operant conflict test) persisted for 1 week or less. An unexpected discovery was latent OA in neurons from thoracic DRGs that innervate dermatomes distant from the injured tissue. The most consistent electrophysiological alteration associated with OA was enhancement of DSFs. Potential in vivo functions of widespread, low-frequency nociceptor OA consistent with these and other findings are to amplify hyperalgesic priming and to drive anxiety-related hypervigilance.

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“…[ 7 ] With the continuous development of anesthetics and related monitoring technologies, the incidence of delayed recovery has been declining year by year, but it is still one of the main complications of general anesthesia. [ 8 ] It not only increases the perioperative risk, affects the recovery of the patient's physical function, but also increases the economic burden of the patient, and even causes death. [ 9 ] Due to the long operation time and the large amount of anesthetic drugs in laparoscopic radical biliary surgery, the risk of DR after surgery also increases.…”

Section: Introductionmentioning

confidence: 99%

“…Delayed recovery (DR) from anesthesia generally refers to that the patient has not recovered 120 minutes after the end of general anesthesia, and cannot respond correctly to external stimuli and language commands [7] . With the continuous development of anesthetics and related monitoring technologies, the incidence of delayed recovery has been declining year by year, but it is still one of the main complications of general anesthesia [8] . It not only increases the perioperative risk, affects the recovery of the patient's physical function, but also increases the economic burden of the patient, and even causes death [9] .…”

Section: Introductionmentioning

confidence: 99%

Risk factors of delayed recovery from general anesthesia in patients undergoing radical biliary surgery

Zhang¹,

Pan²,

Tan³

et al. 2021

Medicine

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Delayed recovery (DR) is very commonly seen in the patients undergoing laparoscopic radical biliary surgery, we aimed to investigate the potential risk factors of DR in the patients undergoing radical biliary surgery, to provide evidences into the management of DR. Patients who underwent radical biliary surgery from January 1, 2018 to August 31, 2020 were identified. The clinical characteristics and treatment details of DR and no-DR patients were compared and analyzed. Multivariable logistic regression analyses were conducted to identify the potential influencing factors for DR in patients with laparoscopic radical biliary surgery. We included a total of 168 patients with laparoscopic radical biliary surgery, the incidence of postoperative DR was 25%. There were significant differences on the duration of surgery, duration of anesthesia, and use of intraoperative combined sevoflurane inhalation (all P < .05), and there were not significant differences on American Society of Anesthesiologists, New York Heart Association, tumor-lymph node- metastasis, and estimated blood loss between DR group and control group (all P > .05). Multivariable logistic regression analyses indicated that age ≥70 years (odd ratio [OR] 1.454, 95% confidence interval [CI] 1.146–1.904), body mass index ≥25 kg/m 2 (OR 1.303, 95% CI 1.102–1.912), alcohol drinking (OR 2.041, 95% CI 1.336–3.085), smoking (OR 1.128, 95% CI 1.007–2.261), duration of surgery ≥220 minutes (OR 1.239, 95% CI 1.039–1.735), duration of anesthesia ≥230 minutes (OR 1.223, 95% CI 1.013–1.926), intraoperative combined sevoflurane inhalation (OR 1.207, 95% CI 1.008–1.764) were the independent risk factors for DR in patients with radical biliary surgery (all P < .05). It is clinically necessary to take early countermeasures against various risk factors to reduce the occurrence of DR, and to improve the prognosis of patients.

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Loss of endogenous analgesia leads to delayed recovery from incisional pain in a rat model of chronic neuropathic pain

Cited by 9 publications

References 37 publications

Rat model of attention-deficit hyperactivity disorder exhibits delayed recovery from acute incisional pain due to impaired descending noradrenergic inhibition

Rat model of attention-deficit hyperactivity disorder exhibits delayed recovery from acute incisional pain due to impaired descending noradrenergic inhibition

Widespread latent hyperactivity of nociceptors outlasts enhanced avoidance behavior following incision injury

Risk factors of delayed recovery from general anesthesia in patients undergoing radical biliary surgery

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