→ 急性胰腺炎治疗方法。疼痛持续时间
急性胰腺炎治疗方法。疼痛持续时间
健康咨询描述：
女，42岁，不知怎么的就突然腹部疼痛不止，恶心呕吐，之后速转入医院治疗。医生诊断为急性胰腺炎。现在人在医院接受治疗，但是疼痛未得缓解。病人呻吟疼痛持续。
曾经的治疗情况和效果：
想得到怎样的帮助：急性胰腺炎这病严重吗？该如何治愈？疼痛时间得持续多久?
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医生回复区
擅长: 妇科肿瘤
消化系统疾病
帮助网友：6522称赞：69
&&&&&&病情分析：&&&&&&胰腺炎如果控制不住，可以导致胰腺的腺体分泌溶解胰腺导致生命危险的，&&&&&&指导意见：&&&&&&必须及时注射专门治疗胰腺炎的药物，配合食物控制，可以好转的，但是病情的恢复是需要时间的，这个不能确定。
擅长: 消化系统疾病，如慢性胃炎，消化性溃疡，肠易激综合症
帮助网友：345称赞：16
&&&&&&病情分析：&&&&&&1.急性胰腺炎临川以上腹部疼痛，多剧烈疼痛难忍，可放射至腰背疼，恶心呕吐，腹胀，发热等为主要表现。&&&&&&
2.急性胰腺炎病因很多常见有，胆结石、饮酒、暴饮暴食、高血脂等。&&&&&&
3.急性胰腺炎是消化道急症重症，应积极性治疗，临床分轻症型胰腺炎和重症型胰腺炎。轻症型胰腺炎多为自限性，积极治疗多能够后很快好转。重症型胰腺炎病情凶险，病死率5%-10%。&&&&&&
4.针对胰腺炎患者腹痛情况，应镇痛治疗，可以应用杜冷丁镇痛。&&&&&&
5.临床胰腺炎治疗主要包括：禁食，营养支持，抑制胰酶活性，抗生素，改善循环等综合治疗。腹胀、恶心呕吐明显的给予胃肠减压。&&&&&&指导意见：&&&&&&1.鉴于患者已经入院治疗，建议积极配合医护人员进行治疗。&&&&&&
2.胰腺炎患者应禁食，所以家属不要觉得患者会饿，擅自给患者喂食等，要不然会加重病情。
擅长: 呼吸、高血压、心脏病、脑血栓
帮助网友：34517称赞：308
&&&&&&病情分析：&&&&&&您好，急性胰腺炎是多种病因导致胰酶在胰腺内被激活后引起胰腺组织自身消化、水肿、出血甚至坏死的炎症反应。临床以急性上腹痛、恶心、呕吐、发热和血胰酶增高等为特点。&&&&&&指导意见：&&&&&&可分为单纯水肿型胰腺炎及出血坏死型胰腺炎2种类型。后者病情凶险，合并症多，死亡率高。不需要手术治疗，抗炎一般7天好转，半个月可以恢复。祝健康。
&&&&&&以上是对“急性胰腺炎治疗方法。疼痛持续时间”这个问题的建议，希望对您有帮助，祝您健康！
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?急性胰腺炎一般会痛多长时间
急性胰腺炎患者可以出现上腹部疼痛，具体疼痛持续时间，要看病情轻重，治疗效果。轻度的胰腺炎，及时治疗的话，大概一两天就会有明显的缓解。如果是重症胰腺炎，治疗不及时，不仅疼痛持续时间长，还会有多器官并发症，甚至危及生命。
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Pain Management in Acute
Pancreatitis
Stephan Schorn, G&ralp O. Ceyhan, Elke Tieftrunk, Helmut Friess
and Ihsan Ekin Demir
Department of Surgery, Klinikum rechts der Isar, Technische
Universit&t M&nchen, Munich, Germany
ekin.demir@tum.de
Entry Version:&
Version 1.0, May 30, 2015
Citation:&
Schorn, Stephan. Ceyhan, G&ralp O. Tieftrunk, Elke. Friess,
Helmut. Demir, Ihsan Ekin. (2015). Pain Management in Acute
Pancreatitis.
Attachment
Severe abdominal pain is a hallmark of acute pancreatitis (AP).
AP-associated pain is often described by patients as a deep and
penetrating type of pain with acute onset and without any prodrome.
Typically, AP patients locate the maximum of pain in the upper
abdomen that radiates like a belt around the trunk into their back.
Pain reaches its maximum severity within hours after its onset and
can last from hours up to days or even months (6, 25, 60, 74, 85).
Therefore, it is not surprising that the presence of persistent
epigastric pain dictates the diagnostic workup of patients
suffering from AP in the clinical routine (6, 25, 29, 46, 85).
Interestingly, beside its diagnostic aid (6), recent studies
suggest pain as a prognostic tool to predict the severity of AP and
the patients’ outcome (40, 60). Nevertheless, an adequate pain
therapy after patients’ admission to hospital is often a
challenging task, which requires interdisciplinary management. In
clinical practice, the treatment of pain ranges and escalates from
low-dose non-opioid analgesics to high-dose opioid analgesics and
even to interventional and surgical approaches.
Introduction
Inflammation of the pancreatic tissue can be divided into
chronic and acute inflammation depending on the degree of
resolution of the tissue inflammation. Over 80% of all cases of AP
are due to gallstones or the alcohol abuse (32, 38, 50).
Severe abdominal pain is the hallmark symptom of patients
suffering from AP as well as of chronic pancreatitis (61, 74, 85).
In AP, the most common localization of acute pain is the epigastric
region (12, 61, 74, 85). Due to the retroperitoneal localization of
the pancreas, it is not unusual that patients describe
AP-associated pain as deep and penetrating. Pain in AP is often
associated with nausea and vomiting. Physical examination yields a
pronounced tenderness of the upper abdomen with guarding, which can
in occur in combination with other unspecific symptoms like fever
or tachycardia.& Maximum pain is typically
localized in the upper epigastric region and radiates like a belt
around the trunk into the back (6, 12, 25). The detection of pain
is a well-accepted diagnostic tool in AP. According to the modified
Atlanta consensus guidelines (6, 12), AP can be diagnosed if at
least two of the following criteria are fulfilled:
The occurrence of abdominal pain that is characterized by an
acute onset and radiates to the back
Serum pancreatic enzymes (lipase or amylase) elevated at least
threefold over& the normal serum enzyme level
Characteristic findings of AP in imaging (contrast-enhanced-CT,
MR-Imaging, transabdominal ultrasound)
2. Role of Pain in
Diagnosis and Prognosis of Patients with AP
Pain is increasingly recognized as a diagnostic and prognostic
factor in AP (1, 2, 6, 40, 60). Interestingly, beside its role in
the diagnosis of AP, more recent studies described the interval
between onset of pain and hospitalization of the patient as an
adequate prognostic factor for estimation of the severity of AP
(40, 60, 61). In a study by Phillip et al., patients with severe
pain had shorter median pain-to-admission time when compared to
patients with only moderate pain (40, 60, 61). Interestingly, the
severity of pain also correlated with the severity of AP in these
two cohorts, and together with serum lipase and C-reactive protein
levels, pain was identified as a predictor of AP (61). The severity
may also allow conclusions on the cause of AP (15, 85). Here, a
genuinely severe abdominal pain preferentially occurs in biliary
AP, whereas alcoholic AP and especially autoimmune pancreatitis are
predominantly accompanied by milder abdominal pain (24, 42,
3. Main Arms of Pain
Management in AP
The successful treatment of patients with AP has three
prerequisites: 1) an adequate and early fluid resuscitation (8, 30,
31, 50), 2) proper nutritional support (48, 50, 86), and 3) an
adequate pain management (5, 45, 50). An effective treatment of
pain in AP ranges from the administration of simple analgesic
drugs, which might be sufficient for patients with mild AP, up to
the administration of potent opioid drugs, high doses of
antibiotics for infected pancreatic necrosis and even to surgical
or interventional procedures in cases of severe AP (1, 7, 9, 25,
27, 41, 46, 50, 51, 74, 85).
Figure 1. The modified World Health Organization
(WHO) analgesia ladder after Vargas-Schaffer
(84). The WHO analgesia
ladder was originally developed to treat pain due to cancer.
However, over time, the indications have been extended, and the
medical management of pain in acute pancreatitis can similarly be
grounded on a modified version of the WHO ladder. Here, persistence
of pain after implementation of a measure of low potency warrants
escalation of analgesia to a more potent substance, which, if there
is ongoing need, can be adjuvantly combined with any measure/agent
from the lower step. This modified ladder includes interventional
procedures that can be indicated once medical measures have failed
to provide adequate analgesia.
However, the whole spectrum of medical, interventional and
surgical possibilities raises the question on how to treat AP
instead of over-treating Treatment of pain may seem to be a simple
task in the clinical routine. Beside the World Health Organization
(WHO) analgesic ladder (Figure 1), which includes
the use of non-steroidal-anti-inflammatory drugs (NSAID) or their
combination with highly potent opioid-analgesics in an escalating
regime (1, 9, 25, 51, 56, 84), the management of abdominal pain
also includes interventional strategies depending on the occurrence
of AP-related complications (15, 16, 27, 29, 35, 38, 46, 64, 76,
80, 85). In fact, the adequate treatment of pain is much more
complex and often needs interdisciplinary action. One reason for
the challenge behind pain management is the high complexity of AP
itself. Whereas mild to moderate epigastric pain is often the
single symptom of edematous pancreatitis, patients with necrotizing
acute pancreatitis often suffer from severe pain attacks, pleural
effusion, ascites and even multiple organ failure. Importantly,
whereas mild AP is rarely lethal (69), the lethality of AP reaches
up to at least 30% in patients with acute, necrotizing pancreatitis
and persistent multiple organ failure (13, 37, 53). Here, as
discussed later in this chapter, more novel analgesic interventions
like thoracic spinal analgesia receive more attention in the
treatment of pain in patients with AP (3, 33).
4. Role of Medical
Treatment in Pain Management during AP
In 1986, the WHO presented the analgesia ladder as a framework
to treat severe pain (56). This ladder was originally developed to
treat pain due to cancer (56). Later, the analgesic pain regime of
the WHO was also assumed to treat pain due to causes other than
cancer (25, 84). According to the WHO regime, the pain treatment
begins with low potent non-steroidal anti-inflammatory medication,
which may be sufficient in mild or moderate pain due to AP (5, 8,
47, 50), and rises step by step up to highly potent NSAIDs alone or
in combination with opioids (56, 84). In the past, the WHO
analgesic ladder was only partially useful for the treatment of AP
patients because opioid analgesics, especially morphine, were long
blamed to cause dysfunction of the sphincter of Oddi after systemic
administration (34). However, several studies showed that morphine
has no proven significantly unfavorable influence on the course of
AP (57). In a comparative study on metamizole (2g/8h i.v.) versus
morphine (10mg/4h subcutaneously/s.c.), metamizole resulted in
somewhat more frequent and quicker pain relief than s.c. morphine
(57). Earlier studies postulated pethidine as the analgesic of
choice in pain due to AP (11). However, Blamey et al. could show
that buprenorphine as a longer-acting analgesic has a similar
analgesic capacity as pethidine, but a lower potential to cause
physical opioid dependence (11).
Indeed, the latest studies including systematic reviews
convincingly demonstrated that opioid analgesics could be safely
administered with major benefit in AP, and that the dogma of “no
opioids in AP” should be considered to be obsolete. To this end,
Jakobs et al. administered 40 patients with acute or acute on
chronic pancreatitis either buprenorphine or procaine as a
continuous intravenous (i.v.) infusion and additional analgesics on
demand (36). Here, patients who received buprenorphine had
significantly less demand after additional analgesics and had lower
visual analogue scale (VAS) pain scores than procaine-receiving
patients, especially during the initial two days of treatment (36).
In another open, randomized, controlled trial including 107 AP
patients, subjects were randomized to receive either procaine
(2g/24hours as continuous i.v. infusion) or pentazocine (bolus i.v.
every 6 hours) (39). Here, patients being treated with procaine
were more likely to demand additional analgesics when compared to
patients receiving pentazocine alone (98% versus 44%) (39).
Furthermore, the pain scores were much higher in the pentazocine
group during the first 3 days of analgesic treatment (39). These
studies therefore provided evidence for the lack of effectiveness
of procaine in AP-associated pain (47).
Overall, there seems currently to be no difference in the risk
of pancreatitis-associated complications or clinically serious
adverse events between opioids and other analgesic agents (9, 36,
73, 77). Particularly, opioid analgesics may be considered an
appropriate choice in the treatment of AP-associated pain, and
importantly, they may decrease the need for supplementary analgesia
5. Role of Nutrition in
Pain Management during AP
One interesting feature of AP-associated pain is potential pain
exacerbation after ingestion of food or fluids (15, 46). This
food-dependent progression of abdominal pain raises the question as
to how far the adequate nutrition therapy also contributes to pain
management. In contrast to the long-believed old paradigm on the
benefits of total parenteral nutrition in AP, Sax et al. could
clearly show that an early, total parenteral feeding of patients
with AP does not provide any benefit with regard to the number of
days to oral intake, total hospital stay, or number of
AP-associated complications (66). Current literature supports the
notion that the right management of nutrition is strongly dependent
on the severity of AP. Importantly in patients with mild to
moderate AP, nasogastric feeding seems to be well tolerated and
might reduce the intensity and the duration of abdominal pain, the
need of pain medication and the risk of oral food intolerance (58).
However, up to now there is no evidence that it might also reduce
the length of hospital stay in these patients (58, 75).
An interesting question on the interaction of pain with
nutrition in AP is related to pain relapse after oral refeeding
during AP. In different studies, the incidence of pain onset or
exacerbation after refeeding ranged between 21-25% and reached a
maximum between 50-100% of cases within 48 h of refeeding (59).
Therefore, the incidence of pain relapse after oral refeeding
during AP seems to be quite high (59). Current evidence suggests
that nutrition support should only be& performed
in patients with severe pancreatitis, whereas nutrition support is
generally not needed in patients with mild or moderate disease
where oral feeding should be started as soon as possible and as
tolerated by patients. If nutrition support is needed in these
patients, enteral nutrition should be preferred over parenteral
nutrition (52). However, a clear consensus on how and when the oral
refeeding should be initiated has not yet been reached. In this
context, Teich et al. reported in their prospective, randomized
study that patients who could decide themselves to start oral
refeeding were able to start oral refeeding one day earlier
compared to patients who received oral nutrition based on the serum
lipase (75). Interestingly, in the self-selected eating group, oral
feeding had no impact on postprandial pain and hospital stay when
compared to lipase-directed decision to oral refeeding.
6. Role of Endoscopic
Retrograde Cholangio-pancreatography (ERCP) in Pain due to
Gallstones are the most common cause of AP in Western and Asian
countries with an incidence reaching up to at least 40% of all AP
cases (15, 20, 72). An important question is how far the removal of
pancreatitis-associated gallstones by ERCP also affects pain
sensation and even more, the morbidity and mortality of AP
patients. It is conceivable that ERCP contributes to adequate pain
management in AP due to removal of the etiological agent. The role
of ERCP in pain management for AP patients is barely described in
current medical literature.
In 2009, Chen et al. demonstrated that patients undergoing ERCP
because of AP may still benefit from concerning pain management
(18). Still, because of its potential complications, there is a
clear consensus on the indication of ERCP in patients with AP. The
single indication for primary therapy via ERCP in AP is suspected
remaining pancreatic or bile duct obstructions or existing
cholangitis (8, 15, 50, 54, 76, 79). Furthermore, ERCP should only
be used for clearance of proven bile duct stones especially in
patients who suffer from severe AP, with clear evidence of
cholangitis, in those who are poor candidates for cholecystectomy,
in those who are post-cholecystectomy, and in those with strong
evidence of persistent biliary obstructions (Table
1). In contrast, ERCP should be avoided in patients with
low or intermediate suspicion of retracted bile duct stones (8, 15,
50, 54, 76, 79). A large meta-analysis by Tse et al. clearly
demonstrated that early ERCP has no clear benefit for patients with
AP compared to an early conservative medical treatment (79).
In conclusion, in the analgesic regime of AP, other non- or less
invasive procedures than ERCP should be preferred to treat pain in
AP. Because of its morbidity and mortality, ERCP should be avoided
as a single analgesic procedure and should only be performed if
there is strong evidence for remaining bile duct stones or
co-existing cholangitis.
7. Role of
Minimally-Invasive Necrosectomy and Decompressive Laparotomy in
Pain due to AP
The management of necrotizing acute pancreatitis has witnessed
considerable progress in recent years. Traditionally, infected
pancreatic necrosis as a result of AP was considered an indication
for open surgical necrosectomy. However, in recent years, an
increasing number of minimally invasive approaches have emerged
that could effectively limit local and systemic damage and thereby,
without the need for open invasive surgery, effectively contribute
to prognostic improvement that is comparable to open necrosectomy.
These approaches, including repetitive percutaneous drainage via
large-caliber catheters (21), endoscopic transluminal necrosectomy
(68), retroperitoneal approach with percutaneous insertion of
endoscopic material (19), and especially a “step-up approach” (82)
have been convincingly shown to decrease the complication rate
associated with necrotic AP. Yet, the long-term outcomes of these
minimally invasive approaches have not yet been sufficiently
investigated. In the GEPARD trial that studied the long-term
outcome of AP patients with endoscopic necrosectomy, 81% of the
patients could be freed from pancreatic necrosis and associated
complications during the first hospital stay (68). From the
long-term survivors, 16% suffered from secondary clinical
recurrence of necrosis or emergence of pseudocysts. Importantly,
all of these 11 patients with recurrence were dependent on regular
intake of analgesic medication, whereas in 6 out of 11 cases, the
intake of analgesics was only occasional (68). In a study that
recently described the long-term outcomes of combined percutaneous
and endoscopic approaches for symptomatic and infected walled-off
necrosis, Ross et al. reported that only 2 out of 117 patients
required late surgery for persistent pain (65). However, this study
did not report on the severity and frequency of pain and on the
analgesic intake of patients who did not require surgery for pain
(65). Overall, these observations imply that the treatment of pain
in necrotic AP via interventional techniques is also dependent on
the overall success of the intervention to resolve AP-associated
complications such as necrosis. On the other hand, persistent pain
despite these minimally invasive approaches seems to guide the
decision toward surgical intervention (62). Patients who have
persistent necrotic collections or pseduocysts seem to be prone
developing chronic abdominal pain, yet the long-term results of all
these interventional approaches are lacking. Moreover, the impact
of these promising procedures on pain sensation does not seem to be
systematically recorded or reported (4).
An approach that was put forward to deal with AP-associated
abdominal hypertension is decompressive laparotomy (81). Abdominal
hypertension is assumed to result from a combination of pancreatic
and visceral edema, acute peripancreatic fluid collections,
capillary leakage, ascites and paralytic ileus, and is encountered
around 27-38% of severe AP cases (81). Abdominal hypertension is
defined by the World Society of Abdominal Compartment Syndrome
(WSACS) as a “life-threatening sustained elevation of the
intraabdominal pressure (IAP) that is associated with new onset
organ failure or acute worsening of existing organ failure” (43).
Thus, elevated IAP is frequently associated with kidney dysfunction
and increased peak airway pressure. However, the question whether
elevated IAP is a direct cause of multi-organ failure or rather a
consequence of organ dysfunction has not yet been answered (78).
Furthermore, when and how to escalate percutaneous drainage to an
aggressive decompressive laparotomy is also yet unclear (81). The
DECOMPRESS trial as a multicenter study will compare percutaneous
catheter drainage with decompressive laparotomy in patients with
elevated IAP during severe AP (63). Until the results of this study
are available, it should be considered that decompressive
laparotomy represents a major invasive intervention with to date no
convincingly proven benefit for treating elevated IAP (22, 78, 81).
Accordingly, how the outcomes of these patients who undergo this
aggressive surgical intervention with regard to long-term
persistence of pain should be addressed in future studies.
8. Novel Strategies of
Pain Management in AP
Beside the above indicated common methods of pain management in
AP, clinical researchers are trying to devise novel analgesic
techniques that interfere in the interaction of the nervous system
with the pancreatitis (Figure 2). In an
interdisciplinary setting, such interventions have been recently
shown to be beneficial not only for pain, but also for the overall
course of the disease.
Figure 2. Management of pain in acute pancreatitis
(AP).Analgesic measures to treat AP-associated pain can be
classified into clinical methods that are in widespread use in
daily clinical practice. The experimental measures have been shown
to be effective in numerous studies with murine or porcine AP
models, yet have not been translated into clinical practice.
To this end, Bachmann et al. recently reported improved survival
owing to thoracic epidural analgesia (TEA) in a porcine AP model
that is based on the infusion of glycodesoxycholic acid into the
pancreatic duct (3).& Here, the 7-day-survival
rate of animals that received bupivacaine as TEA was 82% when
compared to a mere 29% in the control group. This difference was
largely attributable to the improved microcirculation, tissue
oxygenation and consequently preserved microscopic tissue
architecture in the group of pigs that were treated with TEA, with
similar results previously reported for murine AP (23, 28). In a
study on 121 patients admitted to intensive care unit with AP,
Bernhardt et al. reported excellent analgesia on 72% of observation
days during which no systemic use of other analgesics was necessary
(10). The rate of hemodynamic instability (8%) was also low,. The
time to normalization of serum amylase and lipase was 17.4 days
(minimum one day, maximum 19 days), and the overall lethality was
2.5%. In this prospective single cohort study, epidural analgesia
was thus able to produce considerable analgesic effect without any
major rate of complications (10). Therefore, based on these
promising observations, the results of the three clinical trials
that are currently investigating the effect epidural analgesia on
the course of AP are eagerly awaited (70).
Looking at the potential benefits of analgesia, and especially
epidural analgesia with its peripheral neurolytic effects, on the
course of AP, it is essential to remember the contribution of
“neurogenic inflammation” in the pathogenesis of AP. In this
context, different noxious substances released from damaged acini,
i.e. zymogens, trypsin, proteases, ions such as hydrogen or
potassium can activate peripheral nociceptive sensory nerve
endings.& These activated sensory neurons not only
signal centrally toward the spinal cord, but can also
cross-activate other neurons in the neighbouring spinal cord
regions that then signal into the periphery in an antidromic
fashion. This antidromic reflex results in the release of substance
P and calcitonin-gene-related-peptide from the peripheral
nociceptive nerve endings.
These neuropeptides have the intriguing ability to chemoattract
immune cells, cause vasodilatation and thereby augment local
inflammation. In AP, neurogenic inflammation is recognized as a
central pathophysiological event (49). Based on this premise, it is
not surprising to see an analgesic and also overall beneficial
effect of epidural anesthesia on the course of AP. In accordance
with this strategy, inhibitors of the
proteinase-activated-receptor-2 (PAR2), or of the transient
receptor potential vanilloid-1 (TRPV1) have been shown to be
beneficial for treating pain during experimental AP in mice (55).
During experimental AP in rats, intrathecal administration of
gabapentin was reported to enhance the analgesic effects of
subtherapeutic doses of morphine (71). Other targets on neuronal
cells to treat both the inflammation in AP and AP-associated pain
are nitric oxide (NO) signaling and glycine. Treatment of rats with
nitric oxide synthase (NOS) inhibitors (14) or glycine (17) reduced
abdominal hyperalgesia and AP-associated histological alterations
during AP in rats. Recently, blockade of interleukin-6 (IL-6)
signaling by an orally available, small-molecule IL-6 receptor
inhibitor was shown to diminish abdominal hyperalgesia during AP
(83). However, all these promising neuronal targets have not yet
been studied in early phase clinical trials. In the clinical
setting, based on its promising effects during experimental AP in
rats, a promising and inexpensive agent that may used as a novel
analgesic agent is magnesium (67). The MagPEP study as a
multicentre randomized controlled trial of magnesium sulphate in
the prevention of post-ERPC pancreatitis shall provide data on the
impact of magnesium on pain sensation during post-ERCP pancreatitis
(26). Once shown to be effective, beyond its preventive usage,
magnesium may be considered a novel analgesic alternative to treat
pain in AP (26). Overall, the interaction of the nervous system
with pancreatic inflammation may offer numerous clues for more
effective treatment of both the disease itself and the associated
pain. Therefore, efforts toward translating this axis into the
clinical practice need to become more visible in the near
Conclusion
Abdominal pain is the earliest and a leading symptom of patients
with AP. There is solid evidence that the severity of pain may also
predict the clinical course of AP. Treatment of pain during AP
continues to be a challenging task in the clinical routine and
involves a combination of medical treatment according to the WHO
analgesic ladder, adequate nutritional support and, in some cases,
interventional therapy via e.g. ERCP (Table 2).
Novel studies also suggest that the severe abdominal pain in AP
could also be effectively treated by thoracic epidural anesthesia
owing to the improvement of pancreatic microcirculation and
preservation of tissue architecture. Disruption of neurogenic
inflammation in AP holds great promise as a novel analgesic and
therapeutic strategy for AP, which yet needs to be tested in
clinical early phase trials. Development of inhibitors directed
against selected targets on pancreatic afferents is likely to open
new paths toward more effective management of pain as an
interdisciplinary challenge.
Acknowledgements: The authors thank Dr.
Matthias Maak for his valuable assistance in the generation of the
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