Recommendations on practice of conditioned pain modulation (CPM) testing.

Protocols for testing conditioned pain modulation (CPM) vary between different labs/clinics. In order to promote research and clinical application of this tool, we summarize the recommendations of interested researchers consensus meeting regarding the practice of CPM and report of its results.

Negative expectations facilitate mechanical hyperalgesia after high-frequency electrical stimulation of human skin.

BACKGROUND: High-frequency electrical stimulation (HFS) of human skin induces not only an increased pain sensitivity in the conditioning area but also an increased pain sensitivity to mechanical punctate stimuli in the non-conditioned surrounding skin area. The aim of the present study was to investigate whether this heterotopically increased mechanical pain sensitivity can be facilitated through the induction of negative expectations. METHODS: In two independent conditions [a nocebo (n = 15) and control condition (n = 15)], we applied mechanical pain stimuli before, directly after, 10 min and 20 min after HFS in the skin area surrounding the conditioning area, and measured the reported pain intensity [visual analogue scale (VAS)]. All subjects (of both conditions) received a written instruction about the HFS protocol, but only the instruction in the nocebo condition was extended by the following text (in Dutch): 'After the HFS, your skin will become more sensitive to the pinprick stimulation'. RESULTS: Our results clearly show that induced expectations of increased mechanical pain sensitivity after HFS facilitates the reported pain intensity after HFS more than when no information is given. CONCLUSIONS: This study shows for the first time that brain mechanisms, via the induction of negative expectations, can facilitate heterotopic mechanical hyperalgesia after HFS of human skin.

Bilateral thoracoscopic splanchnicectomy for pain in patients with chronic pancreatitis impairs adrenomedullary but not noradrenergic sympathetic function.

BACKGROUND: Bilateral thoracoscopic splanchnicectomy (BTS) is a well-known technique to alleviate intractable pain in patients with chronic pancreatitis. BTS not only disrupts afferent fibers from the pancreas that mediate pain but also postganglionic sympathetic fibers, which originate in segments T5-T12 and which innervate the vasculature of the liver, pancreas, and the adrenal gland. The purpose of this study was to assess whether and how BTS affects sympathetic noradrenergic and adrenomedullary function in patients with chronic pancreatitis. METHODS: Sixteen patients with chronic pancreatitis for at least 1 year underwent autonomic function testing before and 6 weeks after BTS for intractable pain. Testing was performed during supine rest and during sympathetic stimulation when standing. RESULTS: Supine and standing systolic and diastolic blood pressure were significantly lower post-BTS compared with pre-BTS (P = 0.001). One patient showed orthostatic hypotension after BTS. Baseline plasma norepinephrine levels and plasma norepinephrine responses to sympathetic activation during standing were not reduced by BTS. In contrast, supine plasma epinephrine levels and responses during standing were significantly reduced (P < 0.001). Parasympathetic activity was unaffected by BTS as shown by unaltered Valsalva ratio, I-E difference, and ΔHRmax. CONCLUSIONS: BTS for pain relief in patients with chronic pancreatitis reduced adrenomedullary function, due to disruption of the efferent sympathetic fibers to the adrenal gland. BTS did not affect noradrenergic sympathetic activity, although blood pressure was lower after the sympathectomy.

Increased sympathetic activity in chronic pancreatitis patients is associated with hyperalgesia.

Pain treatment in chronic pancreatitis patients is difficult, with pain frequently relapsing or persisting. Recent studies suggest that altered central nervous system pain processing underlies the chronic pain state in these patients. There is evidence that increased sympathetic activity may also play a role in some chronic pain syndromes. This study assessed sympathetic nervous system activity and its relation to pain processing in patients with severe painful chronic pancreatitis. The authors postulated that chronic pancreatitis patients with more sympathetic activity exhibit more generalized hyperalgesia. In 16 chronic pancreatitis patients, sympathetic activity was measured via venous plasma norepinephrine (NE) levels (supine, standing). Pain processing was quantified via pressure pain tolerance thresholds (PPTs) in dermatomes T10 (pancreatic area), C5, T4, L1. Five patients showed increased supine plasma NE levels (NE ≥ 3.0 nmol/L). PPTs were lower in patients with increased NE levels (INE) compared with patients with normal NE (NNE) (means [95% confidence interval]: INE 402 kPa [286-517] versus NNE 522 kPa [444-600]; P = .042). In severe chronic pancreatitis patients, increased sympathetic activity and hyperalgesia appear associated, suggesting that sympathetic activity may also play a role in these patients' pain.

Effect of thoracoscopic splanchnic denervation on pain processing in chronic pancreatitis patients.

BACKGROUND: Central sensitisation due to visceral pancreatic nociceptive input may play an important role in chronic pancreatitis pain. Using quantitative sensory testing (QST), this first study investigates whether thoracoscopic splanchnic denervation (TSD), performed to reduce nociceptive visceral input, affects central sensitisation in chronic pancreatitis patients. PATIENTS AND METHODS: We studied 19 chronic pancreatitis patients (11 men, 8 women on stable opioid medication) and 18 healthy volunteers as preoperative controls. Preoperatively and 6 weeks after TSD, pain numeric rating scores, opioid medication, and thresholds to electric skin stimulation and pressure pain (measured in dermatomes T10 (pancreas), C5, T4, L1, L4) were documented. Treatment success was defined as cessation of opioids 6 weeks after TSD. RESULTS: Six weeks after TSD, there was a trend towards lower pain scores, only 10 patients were still on opioids (P<0.05 vs. preoperatively) and thresholds overall were significantly higher than preoperatively (pressure pain: +25%, P<0.001; electric: sensation +55%, pain detection +34%, pain tolerance +21%, P<0.05). Gender-specific differences in hypoalgesia patterns were seen. Preoperatively, TSD treatment successes consumed significantly less opioids than failures, without significant differences in preoperative patterns of neuroplasticity. CONCLUSIONS: TSD for chronic pancreatitis pain resulted in fewer patients on opioids and overall increases in pain thresholds. Our results suggest that TSD for reducing visceral nociceptive input may be effective in reducing resulting central sensitisation. Although patients benefiting from TSD consume less opioids preoperatively, we were unable to clearly link treatment success with specific perioperative patterns of neuroplasticity such as the presence or absence of hyperalgesia.

Chronic post-thoracotomy pain: a retrospective study.

BACKGROUND: Chronic pain is common after thoracotomy. The primary goal of this study was to investigate the incidence of chronic post-thoracotomy pain. The secondary goal was to identify possible risk factors associated with the development of chronic post-operative pain. METHODS: We contacted 255 patients who had undergone a classic postero-lateral thoracotomy at our institution in the period between January 2001 and December 2003. All patients received a letter requesting participation; a questionnaire was included with the letter. One week later patients were contacted by telephone to obtain the answers to the questionnaire. RESULTS: We ultimately obtained results from 149 patients (58% of all thoracotomies, 84% of survivors). The overall incidence of chronic post-operative pain was 52% (32% mild, 16% moderate and 3% severe chronic post-operative pain). Patients with chronic post-operative pain reported acute post-operative pain more frequently than those without (85% vs. 62%, P = 0.01), had more severe acute post-operative pain (P = 0.0001), underwent more extensive surgical procedures (P = 0.01), had more constant acute pain (vs. fluctuating pain or pain in attacks) (P = 0.0004) and reported less absence of pain during the first post-operative week (P = 0.0001). There was no significant decrease in chronic pain with time after thoracotomy. CONCLUSION: Our study confirms that chronic post-thoracotomy pain is a common problem. The results from our study suggest that chronic post-thoracotomy pain may be associated with more intensive and extensive nociceptive input due to thoracic surgery.

Pharmacological management of pain in chronic pancreatitis.

Pain is the major presenting symptom of chronic pancreatitis. Patients with chronic pancreatitis experience substantial impairments in health-related quality of life. Pain may be considered as the most important factor affecting the quality of life. The pathogenesis of pancreatic pain is poorly understood. The cause of pain in chronic pancreatitis is probably multifactorial. This article discusses the various hypotheses that have been suggested to underlie pain. Special attention is paid to the concept of autonomous central sensitisation and hyperalgesia as a cause of pain. Strict abstinence from alcohol is the first step of chronic pancreatic pain management. As a second step, it is important to exclude treatable complications of chronic pancreatitis, such as pseudocysts. Symptomatic treatment with analgesics is often unavoidable in patients with chronic pancreatitis. Acetaminophen, non-steroidal anti-inflammatory drugs and eventually opioids are suitable. Several trials have been performed with pancreatic enzymes, but a meta-analysis demonstrated no significant benefit in terms of pain relief. The treatment of chronic pancreatic pain requires a multidisciplinary approach that tailors the various therapeutic options to meet the need of the individual patient.

Do diagnostic segmental nerve root blocks in chronic low back pain patients with radiation to the leg lack distinct sensory effects? A preliminary study.

BACKGROUND: The present preliminary study documents the effects of a selective nerve root block (SNB) with short or long acting local anaesthetic compared with baseline measurements in patients with chronic low back pain radiating to the leg with maximum pain in one dermatome (L4). METHODS: Ten consecutive patients underwent 20 controlled SNBs at L4 with ropivacaine 0.25% and lidocaine 1% in a prospective, randomized, double blind, crossover fashion. Baseline measurements included sensory function (assessed by pinprick on both unaffected and painful leg) and pain (Verbal Numeric Rating Scale; VNRS, 0-10). A change in size of areas with altered sensory function >10% and a VNRS change of 2 points were considered clinically significant. P-values<0.05 were considered statistically significant. RESULTS: Asymptomatic hypoaesthesia, variable in extent and non-dermatomal in distribution, was present in seven patients at baseline. It appeared to be more extensive and distal with longer duration of pre-existing pain. SNB produced no consistent changes in extent and distribution of hypoaesthetic areas. Change in VNRS did not correlate with the extent of pre-block or post-block hypoaesthesia. No differences in effects were found between lidocaine and ropivacaine. CONCLUSIONS: Pre-block assessment of sensory function is essential to assess the net effect of SNBs. In this small study group, SNBs failed to demonstrate uniform or distinct effects on sensory function.