Loss of GABA-mediated inhibition in the spinal cord is thought to mediate allodynia and spontaneous pain after nerve injury. Despite extensive investigation of GABA itself, relatively little is known about how nerve injury alters the receptors at which GABA acts. This study examined levels of GABA(B) receptor protein in the spinal cord dorsal horn, and in the L4 and L5 (lumbar designations) dorsal root ganglia one to 18 weeks after L5 spinal nerve ligation. Mechanical allodynia was maximal by 1 week and persisted at blunted levels for at least 18 weeks after injury. Spontaneous pain behaviors were evident for 6 weeks. Western blotting of dorsal horn detected two isoforms of the GABA(B(1)) subunit and a single GABA(B(2)) subunit. High levels of GABA(B(1a)) and low levels of GABA(B(1b)) protein were present in the dorsal root ganglia. However, GABA(B(2)) protein was not detected in the dorsal root ganglia, consistent with the proposed existence of an atypical receptor composed of GABA(B(1)) homodimers. The levels of GABA(B(1a)), GABA(B(1b)), and GABA(B(2)) protein in the ipsilateral dorsal horn were unchanged at any time after injury. Immunohistochemical staining also did not detect a change in GABA(B(1)) or GABA(B(2)) subunits in dorsal horn segments having a robust loss of isolectin B4 staining. The levels of GABA(B(1a)) protein were also unchanged in the L4 or L5 dorsal root ganglia at any time after spinal nerve ligation. Levels of GABA(B(2)) remained undetectable. Finally, baclofen-stimulated binding of guanosine-5'-(gamma-O-thio)triphosphate in dorsal horn did not differ between sham and ligated rats. Collectively, these results argue that a loss of GABA(B) receptor-mediated inhibition, particularly of central terminals of primary afferents, is unlikely to mediate the development or maintenance of allodynia or spontaneous pain behaviors after spinal nerve injury.
Pancreatic and other upper abdominal organ malignancies can produce intense visceral pain syndromes that are frequently treated with splanchnic nerve neurolysis (SNN) or celiac plexus neurolysis (CPN). Although commonly performed with either alcohol or phenol, there is scant literature on the comparative effectiveness, duration of benefit, and complication profile comparing the 2 agents. This study presents a retrospective chart review of 93 patients who underwent SNN for cancer-related abdominal pain in order to describe patient characteristics, examine comparative efficacy, duration of benefit, and incidence of complications with alcohol vs. those of phenol. Consistent with previous studies, SNN reduced reported pain scores while not significantly reducing opioid consumption. No difference in pain outcomes was found comparing alcohol versus phenol based neurolytic techniques. Celiac axis tumor infiltration and pre-procedural local radiation therapy did not change the effectiveness of the procedure. Our data demonstrated that 44.57% of patients had ≥ 30% pain reduction while 43.54% did not have pain reduction. Interestingly, the procedure produced significant improvements in anxiety, depression, difficulty thinking clearly, and feeling of well-being. In addition, no difference in complications was seen between the agents either. SNN was an effective and relatively safe procedure for the treatment of pain associated with pancreatic and other upper abdominal organ malignancies in our sample of patients. Choice of neurolytic agent can appropriately be left to the clinical judgment and local availability of the treating physician. The change in ancillary symptoms has a theoretical basis that supports a biopsychosocial model of pain since changes in one target area (pain) impact other related ones (depression and anxiety). Key words: Celiac plexus, splanchnic nerves, neurolysis, nerve block, alcohol, ethanol, phenol, pain, cancer pain, abdominal pain, visceral pain, symptom assessment
History of ETOH use, anxiety, high SOAPP-SF score, and younger age were associated with UDT that indicates noncompliance. Given the very small percentage of UDT testing, it is quite likely that a significant number of patients who did not undergo UDT were also nonadherent with treatment recommendations.
The last several decades have seen a marked increase in both the recognition and treatment of chronic pain. Unfortunately, patients frequently misunderstand both the nature of pain and the best practices for its treatment. Because primary care physicians treat the majority of chronic pain, they are ideally situated to provide evidence-based pain care. The majority of the medical evidence supports a biopsychosocial model of pain that integrates physical, emotional, social, and cultural variables. The goal of this primer is to assist primary care physicians in their understanding of pain, evaluation of the chronic pain patient, and ability to direct evidence-based care. This article will discuss the role of physical rehabilitation, pain psychology, pharmacotherapy, and procedural interventions in the treatment of chronic pain. Given the current epidemic of drug-related deaths, particular emphasis is placed on the alternatives to opioid therapy. Unfortunately, death is not the only significant complication from opioid therapy, and this article discusses many of the most common side effects. This article provides general guidelines on the most appropriate utilization of opioids with emphasis on the recent Centers for Disease Control and Prevention guidelines, risk stratification, and patient monitoring. Finally, the article concludes with the critical role that a pain medicine specialist can play in the management of patients with chronic pain.
This study examined the distribution of γ-aminobutyric acid (GABA)B receptors on immunohistochemically identified neurons, and levels of GABAB(1) and GABAB(2) mRNA, in the L4 and L5 dorsal root ganglia (DRG) of the rat in the absence of injury and 2 weeks after L5 spinal nerve ligation. In uninjured DRG, GABAB(1) immunoreactivity colocalized exclusively with the neuronal marker (NeuN) and did not colocalize with the satellite cell marker S-100. The GABAB(1) subunit colocalized to >97% of DRG neurons immunoreactive (IR) for neurofilament 200 (N52) or calcitonin gene-related peptide (CGRP), or labeled by isolectin B4 (IB4). Immunoreactivity for GABAB(2) was not detectable. L5 spinal nerve ligation did not alter the number of GABAB(1)-IR neurons or its colocalization pattern in the L4 DRG. However, ligation reduced the number of GABAB(1)-IR neurons in the L5 DRG by ≈38% compared with sham-operated and naïve rats. Specifically, ligation decreased the number of CGRP-IR neurons in the L5 DRG by 75%, but did not decrease the percent colocalization of GABAB(1) in those that remained. In the few IB4-positive neurons that remained in the L5 DRG, colocalization of GABAB(1)-IR decreased to 75%. Ligation also decreased levels of GABAB(1) and GABAB(2) mRNA in the L5, but not the L4 DRG compared with sham-operated or naïve rats. These findings indicate that the GABAB receptor is positioned to presynaptically modulate afferent transmission by myelinated, unmyelinated, and peptidergic afferents in the dorsal horn. Loss of GABAB receptors on primary afferent neurons may contribute to the development of mechanical allodynia after L5 spinal nerve ligation.
Objective To determine if focal increased uptake at the rotator interval (RI) and/or inferior capsule (IC) on 18F-FDG PET/CT (“positive PET”) predicts the presence of adhesive capsulitis (AC). Materials and Methods Three populations were retrospectively examined. Group 1 included 1,137 consecutive 18F-FDG PET/CT studies and was used to determine the prevalence of focal uptake at the RI or IC. Group 2 included 361 cases from a 10-year period with 18F-FDG PET/CT and MRI of shoulder performed within 45 days of each other and was used to enrich the study group. Group 3 included 109 randomly selected patients from the same time frame as groups 1 and 2 and was used to generate the control group. The study group consisted of 15 cases from the 3 groups, which had positive PET findings. PET/CT images were assessed in consensus by two musculoskeletal radiologists. The reference standard for a diagnosis of AC was clinical and was made by review of the medical record by a pain medicine physician. Results The prevalence of focal activity at either the RI or IC (“positive PET”) was 0.53%. Nine patients had a clinical diagnosis of AC and 15 patients had a positive PET. The sensitivity and specificity of PET for detection of AC was 56% and 87%, respectively. PET/CT had a positive likelihood ratio for AC of 6.3 (95% CI: 2.8–14.6). Conclusion Increased uptake at the RI or IC on PET/CT confers a moderate increase in the likelihood of AC.
Background: Intrathecal drug delivery (IDD) and spinal cord stimulator (SCS) systems are implantable devices for the management of both chronic and cancer pain. Although these therapies have favorable long-term outcomes, they are associated with occasional complications including infection. The incidence of infectious complications varies from 2 - 8% and frequently requires prolonged antibiotics and device revision or removal. Cancer patients are particularly susceptible to infectious complications because they are immunocompromised, malnourished, and receiving cytotoxic cancer-related therapies. Objective: Determine if cancer pain patients have a higher incidence of infectious complications following implantation of IDD or SCS systems than non-cancer pain patients. Study Design: Retrospective chart review. Setting: Single tertiary comprehensive cancer hospital. Methods: Following local Institutional Review Board (IRB) approval, we collected data on infectious complications for IDD and SCS systems implanted at MD Anderson Cancer Center for the treatment of cancer and chronic pain. The examined implants were performed from July 15, 2006, to July 14, 2009. In addition, we obtained data regarding patient comorbidities and perioperative risk factors to assess their impact on infectious complications. Results: One hundred forty-two devices were implanted in 131 patients during the examined period. Eighty-three of the devices were IDD systems and 59 were SCS systems. Eighty percent of the patients had a diagnosis of cancer. Four infectious complications were noted with an overall infectious risk of 2.8%. The infection rate was 2.4% for IDD systems versus 3.4% for SCS systems (P = 1). All infections were at the implantable pulse generator (IPG) or pump pocket site. The rate of infection was 2.7% for cancer patients and 3.3% for non-cancer patients (P = 1). Neither the perioperative administration of prophylactic antibiotics (P = 0.4) nor the National Nosocomial Infection Surveillance (NNIS) risk level for individual patients (P = 0.15) were statistically associated with infectious complication. The mean surgical time was longer for cases with infection at 215 ± 93 minutes versus 132 ± 52 minutes for those without infection which was statistically significant (P = 0.02). Limitations: The major limitation of this study is that it was a retrospective analysis. An additional limitation is that 51(38.9%) of our patients either died or were lost to follow-up during the year following implantation which may have led to an underestimation of our infection rates. Conclusions: The experience of this tertiary cancer pain center demonstrates that infectious complications following implantation of IDD and SCS systems are relatively rare events in cancer patients. Contrary to our initial hypothesis, no difference was found in the infection rate between cancer and non-cancer patients. The main factor associated with increased risk of infectious complications was increased surgical time, indicating a need to minimize patient time in the operating room. The low infectious complication rate seen in this series compared to previous reports in non-cancer patients is likely multifactorial in nature. Key Words: Spinal cord stimulation, intrathecal drug delivery, implantable pain therapies, neuromodulation, pain procedures, pain, complications, infection, surgical site infection
Background: Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) have sufficient scientific support for their use as tissue protectors. Preliminary studies suggest that their angiotensin-II type 2 receptor (AT2R)-blocking properties have a beneficial profile in the treatment of neuropathic pain. Objectives: The purpose of the current study was to quantify the extent of the somatosensory effects of ACEI and ARB in cancer patients with chemotherapy-induced peripheral neuropathy. Study Design: We performed a retrospective review of cancer patients with peripheral neuropathy of the upper limbs induced by known neurotoxic anti-cancer agents. Setting: Pain Medicine department at academic tertiary care cancer center. Methods: Using our quantitative sensory testing (QST) data bank, we retrospectively compared the tactile function and the touch, sharp, and thermal thresholds of patients who were previously receiving ACEI or ARB for high blood pressure with these variables in controls who were not receiving ACEI or ARB. Results: Of the 209 patients available for analysis, 145 met inclusion criteria. Baseline characteristics of patients included were generally similar. We identified 29 patients who were receiving AT2R inhibitors prior to starting chemotherapy. Touch thresholds were statistically lower in the thenar aspect of hand in the study group (patients who received AT2R inhibitors) than in the control group [mean (± SD), median 3.03 g (± 11.05), median 0.56 g and 6.75 g (± 18.28), 0.56 g, respectively (P = 0.0441)]. Similarly, the cold pain threshold was statistically higher at the thenar area for the study group [mean (± SD), median 13.23°C (± 8.02), 11.73°C] than for controls [9.89°C (± 6.62), 10.05°C (P = 0.0369)]. Limitations: Inadequacies in the original data acquisition and documentation of the QST and the medical records could not be addressed due to the retrospective nature of the study. Similarly, a discrepancy on the size of the comparison groups could not be reconciled. In addition, based on the available information and the lack of documented concomitant pain levels, we did not find an objective parameter able to correlate the QST findings with pain levels. Conclusions: AT2R inhibitors might offer partial and selective neuroprotective qualities of the myelinated fibers A-β and A-δ in cancer patients who receive neurotoxic chemotherapy. Key words: Quantitative sensory testing, chemotherapy-induced peripheral neuropathy, angiotensin-II type 2 receptor (AT2R)
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