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Is There a Link Between Acute Pain and Chronic Pain?
Abstract
Pain is a normal physiologic response to injury. The presence of pain signals impending tissue injury and signals the need to protect the injured area during healing. Under some circumstances, pain persists after all tissue has healed. We now have a detailed understanding of the physiologic mechanisms that are responsible for the initial perception of acute pain and the neuronal changes that rapidly lead to an increase in sensitivity of the injured region. At the same time, efforts to use combinations of analgesics and analgesic techniques including regional analgesia have been closely studied and shown to provide excellent pain relief. Despite our best efforts, some patients go on suffer from long-term chronic pain after the acute event. In this review, we will examine the basic physiologic mechanisms that lead to the perception of acute pain, our current understanding of the neuronal mechanisms that produce sensitization immediately after injury, and the risk factors that are associated with persistent pain after surgery. Our discussion will include an examination of the role for specific analgesic techniques in improving pain control in the immediate postoperative period and how we might identify those at greatest risk for persistent pain and develop analgesic regimens most likely to minimize the risk of persistent pain.
... These areas heal poorly without the normal protective reminder that pain provides, often leading to amputation. Also, poorly healing decubitus ulcers that occur in patients who have sustained spinal cord injury are another example of the importance of normal sensation and pain in reminding us to protect injured areas so that healing can proceed without recurrent injury (Rathmell, 2012). However, when pain becomes chronic that is when subjects live with unrelenting pain over many years, it becomes maladaptive and modifies one's outlook to everyday experience and to future expectations, by changing physiological and psychological processes underlying pain perception and pain-related behavior (Baliki et al., 2006). ...
Synthetic analgesic and anti-inflammatory drugs have major side effects such as constipation, nausea, vomiting, sedation, mental clouding, etc., which have significantly limited their use. There is therefore, an intensification of search for newer analgesic and anti-inflammatory agents from the huge array of medicinal plant resources with better efficacy and fewer side effect profiles. Medicinal plants such as Olax subscorpioidea have been used traditionally for the management of pains, inflammatory diseases, yellow fever, cancer and rheumatism. The study aims at establishing the analgesic and anti-inflammatory potentials of methanol leaf extract of Olax subscorpioidea; and elucidating its possible mechanism of analgesic and anti-inflammatory actions.
The results of the studies revealed that Olax subscorpioidea possesses marked analgesic and anti-inflammatory activities; the anti-inflammatory activity is mediated via the inhibition of pro-inflammatory cytokines such as IL-1α, IL-1β, VEGF and EGF and/or via the stimulation of the synthesis of anti-inflammatory cytokines such as IL-5, IL-6 and IFN-γ. These results also suggest the possible involvement of serotonergic and nitric oxide pathways in the analgesic effect of Olax subscorpioidea.
... Nowadays, in human adult 50-70 billion cells tolerate apoptosis which is considered as an innovative cells in self-renewing tissue 3 , Apoptosis is an essential device of cell death equally in HF and cardiac ischemia; though, the causal apparatuses through which the heart loses myocytes in HF remain entirely doubtful 4-6 . Consequently, apoptosis was steadily distinguished in MI, LVH, ischemia, ischemia-reperfusion, calcium excess, oxidative stress, gene induction, sustained stretching and doxorubicin use in investigational models of HF 7 . These studies recommend the frequency concerning the existence of apoptosis which can differ extensively as a turning point proceeding the model which is also considered the area of risk to be surveyed 8 . ...
Noxious skin stimuli which are sufficiently intense to produce tissue injury, characteristically generate prolonged post-stimulus sensory disturbances that include continuing pain, an increased sensitivity to noxious stimuli and pain following innocuous stimuli. This could result from either a reduction in the thresholds of skin nociceptors (sensitization) or an increase in the excitability of the central nervous system so that normal inputs now evoke exaggerated responses. Because sensitization of peripheral receptors occurs following injury, a peripheral mechanism is widely held to be responsible for post-injury hypersensitivity. To investigate this I have now developed an animal model where changes occur in the threshold and responsiveness of the flexor reflex following peripheral injury that are analogous to the sensory changes found in man. Electrophysiological analysis of the injury-induced increase in excitability of the flexion reflex shows that it in part arises from changes in the activity of the spinal cord. The long-term consequences of noxious stimuli result, therefore, from central as well as from peripheral changes.
Acute postoperative pain is followed by persistent pain in 10-50% of individuals after common operations, such as groin hernia repair, breast and thoracic surgery, leg amputation, and coronary artery bypass surgery. Since chronic pain can be severe in about 2-10% of these patients, persistent postsurgical pain represents a major, largely unrecognised clinical problem. Iatrogenic neuropathic pain is probably the most important cause of long-term postsurgical pain. Consequently, surgical techniques that avoid nerve damage should be applied whenever possible. Also, the effect of aggressive, early therapy for postoperative pain should be investigated, since the intensity of acute postoperative pain correlates with the risk of developing a persistent pain state. Finally, the role of genetic factors should be studied, since only a proportion of patients with intraoperative nerve damage develop chronic pain. Based on information about the molecular mechanisms that affect changes to the peripheral and central nervous system in neuropathic pain, several opportunities exist for multimodal pharmacological intervention. Here, we outline strategies for identification of patients at risk and for prevention and possible treatment of this important entity of chronic pain.
Despite the enormous success of total knee arthroplasty (TKA), chronic neuropathic pain can develop postoperatively and is both distressing and difficult to treat once established. We hypothesized that perioperative treatment with pregabalin, a chronic pain medication, would reduce the incidence of postsurgical neuropathic pain.
We performed a randomized, placebo-controlled, double-blind trial of pregabalin (300 mg) administered before TKA and for 14 days after TKA (150-50 mg twice daily). Patients were screened for the presence of neuropathic pain at 3 and 6 mo postoperatively using the Leeds Assessment of Neuropathic Symptoms and Signs scale. Secondary outcomes included postsurgical recovery and rehabilitation measures, including knee range of motion, opioid consumption, postoperative pain scores, sleep disturbance, and time to discharge as well as the occurrence of postoperative systemic complications.
Of the 240 patients randomly assigned to the 2 treatment groups (120 in each), data for the primary outcome were obtained from 113 pregabalin patients and 115 placebo patients. At both 3 and 6 mo postoperatively, the incidence of neuropathic pain was less frequent in the pregabalin group (0%) compared with the placebo group (8.7% and 5.2% at 3 and 6 mo, respectively; P = 0.001 and P = 0.014). Patients receiving pregabalin also consumed less epidural opioids (P = 0.003), required less oral opioid pain medication while hospitalized (P = 0.005), and had greater active flexion over the first 30 postoperative days (P = 0.013). There were no differences in the actual recorded duration of hospitalization between the 2 groups, although time to achieve hospital discharge criteria was longer for placebo patients, 69.0 +/- 16.0 h (mean +/- SD), than that of pregabalin patients, 60.2 +/- 15.8 h (P = 0.001). Sedation (P = 0.005) and confusion (P = 0.013) were more frequent on the day of surgery and postoperative day 1 in patients receiving pregabalin.
Perioperative pregabalin administration reduces the incidence of chronic neuropathic pain after TKA, with less opioid consumption and better range of motion during the first 30 days of rehabilitation. However, in the doses tested, it is associated with a higher risk of early postoperative sedation and confusion.
This qualitative and quantitative systematic review of preemptive analgesia did not provide any evidence of timing of single-dose or continuous postoperative pain treatment to be of importance for postoperative analgesia.
Whether preemptive analgesic interventions are more effective than conventional regimens in managing acute postoperative pain remains controversial. We systematically searched for randomized controlled trials that specifically compared preoperative analgesic interventions with similar postoperative analgesic interventions via the same route. The retrieved reports were stratified according to five types of analgesic interventions: epidural analgesia, local anesthetic wound infiltration, systemic N-methyl-d-aspartic acid (NMDA) receptor antagonists, systemic nonsteroidal antiinflammatory drugs (NSAIDs), and systemic opioids. The primary outcome measures analyzed were the pain intensity scores, supplemental analgesic consumption, and time to first analgesic consumption. Sixty-six studies with data from 3261 patients were analyzed. Data were combined by using a fixed-effect model, and the effect size index (ES) used was the standardized mean difference. When the data from all three outcome measures were combined, the ES was most pronounced for preemptive administration of epidural analgesia (ES, 0.38; 95% confidence interval [CI], 0.28-0.47), local anesthetic wound infiltration (ES, 0.29; 95% CI, 0.17-0.40), and NSAID administration (ES, 0.39; 95% CI, 0.27-0.48). Whereas preemptive epidural analgesia resulted in consistent improvements in all three outcome variables, preemptive local anesthetic wound infiltration and NSAID administration improved analgesic consumption and time to first rescue analgesic request, but not postoperative pain scores. The least proof of efficacy was found in the case of systemic NMDA antagonist (ES, 0.09; 95% CI, -0.03 to 0.22) and opioid (ES, -0.10; 95% CI, -0.26 to 0.07) administration, and the results remain equivocal.
As a broader definition of preemptive analgesia, preventive analgesia aims to prevent the sensitization of central nervous system, hence the development of pathologic pain after tissular injury. To demonstrate benefits from preventive treatment, objective measurement of postoperative pain such as wound hyperalgesia and persistent pain should be evaluated. The current study assessed the role and timing of epidural analgesia in this context.
In a randomized, double-blinded trial, 85 patients scheduled to undergo neoplastic colonic resection were included. All the patients received a thoracic epidural catheter, systemic ketamine at a antihyperalgesic dose, and general anesthesia. Continuous infusion of analgesics belonging to the same class was administered by either intravenous or epidural route before incision until 72 h after surgery. Patients were allocated to four groups to receive intraoperative intravenous lidocaine-sufentanil-clonidine or epidural bupivacaine-sufentanil-clonidine followed postoperatively by either intravenous (lidocaine-morphine-clonidine) or epidural (bupivacaine-sufentanil-clonidine) patient-controlled analgesia. Postoperative pain scores (visual analog scale), analgesic consumption, wound area of punctuate hyperalgesia, residual pain, and analgesics needed from 2 weeks until 12 months were recorded.
Analgesic requirements, visual analog scale scores, and area of hyperalgesia were significantly higher in the intravenous treatment group (intravenous-intravenous), and more patients reported residual pain from 2 weeks until 1 yr (28%). Although postoperative pain measurements did not differ, postoperative epidural treatment (intravenous-epidural) was less effective to prevent residual pain at 1 yr (11%; P = 0.2 with intravenous-intravenous group) than intraoperative one (epidural-epidural and epidural-intravenous groups) (0%; P = 0.01 with intravenous-intravenous group).
Combined with an antihyperalgesic dose of ketamine, intraoperative epidural analgesia provides effective preventive analgesia after major digestive surgery.
We report that GTP cyclohydrolase (GCH1), the rate-limiting enzyme for tetrahydrobiopterin (BH4) synthesis, is a key modulator of peripheral neuropathic and inflammatory pain. BH4 is an essential cofactor for catecholamine, serotonin and nitric oxide production. After axonal injury, concentrations of BH4 rose in primary sensory neurons, owing to upregulation of GCH1. After peripheral inflammation, BH4 also increased in dorsal root ganglia (DRGs), owing to enhanced GCH1 enzyme activity. Inhibiting this de novo BH4 synthesis in rats attenuated neuropathic and inflammatory pain and prevented nerve injury-evoked excess nitric oxide production in the DRG, whereas administering BH4 intrathecally exacerbated pain. In humans, a haplotype of the GCH1 gene (population frequency 15.4%) was significantly associated with less pain following diskectomy for persistent radicular low back pain. Healthy individuals homozygous for this haplotype exhibited reduced experimental pain sensitivity, and forskolin-stimulated immortalized leukocytes from haplotype carriers upregulated GCH1 less than did controls. BH4 is therefore an intrinsic regulator of pain sensitivity and chronicity, and the GTP cyclohydrolase haplotype is a marker for these traits.
Review article: Preventive analgesia: quo vadimus?
- Katz