Interventional techniques in the management of chronic pain: Part 2.0.

The practice guidelines for interventional techniques in the management of chronic pain are systematically developed statements to assist physician and patient decisions about appropriate health care related to chronic pain. These guidelines are professionally derived recommendations for practices in the diagnosis and treatment of chronic or persistent pain. They were developed utilizing a combination of evidence and consensus based techniques, to increase patient access to treatment, improve outcomes and appropriateness of care, and optimize cost-effectiveness. The guidelines include a discussion of their purpose, rationale, and importance, including the patient population served, the methodology and the pathophysiologic basis for intervention. Various interventional techniques will be discussed addressing the rationale for their use in chronic pain with analysis of the outcomes data and cost effectiveness. These guidelines do not constitute inflexible treatment recommendations. It is expected that a provider will establish a plan of care on a case-by-case basis, taking into account an individual patient's medical condition, personal needs, and preferences, and the physician's experience. Based on an individual patient's needs, treatment different from that outlined here could be warranted.

Effectiveness of lumbar facet joint nerve blocks in chronic low back pain: a randomized clinical trial.

This randomized clinical trial was designed to determine the effectiveness of therapeutic lumbar facet joint nerve blocks. Two hundred patients were evaluated with controlled diagnostic blocks for the presence of facet joint mediated pain. Eighty four patients, or 42% were determined to have lumbar facet joint mediated pain. These patients were randomly allocated into two groups: Group I receiving therapeutic injections with local anesthetic and Sarapin, and Group II receiving therapeutic injections with a mixture of local anesthetic, Sarapin, and methyl prednisolone. A total of 73 patients were treated with medial branch blocks under fluoroscopy. Results showed that patients underwent multiple procedures over a period of 2(1/2) years. The mean number of procedures or interventions was 2.5 +/- 0.09 from 1 to 3 months, whereas it was 4 +/- 0.13 for 4 to 6 months, 6.1 +/- 0.21 for 7 to 12 months, and 8.4 +/- 0.31 for 13 to 32 months. Cumulative significant relief with one to three injections was 100% up to 1 to 3 months, 82% for 4 to 6 months, 21% for 7 to 12 months, and 10% after 12 months, with a mean relief of 6.5 +/- 0.76 months. There was significant improvement noted in overall health status with improvement not only in pain relief, but also with physical, functional, and psychological status, as well as return-to-work status. In conclusion, the results of this study demonstrate that medial branch blocks with local anesthetic and Sarapin, with or without steroids, are a cost effective modality of treatment, resulting in improvement in pain status, physical status, psychological status, functional status and return to work.

The diagnostic validity and therapeutic value of lumbar facet joint nerve blocks with or without adjuvant agents.

Facet joints have been described as an important source of low back pain. The value of medial branch blocks in the diagnosis of facet joint mediated pain is considered important. However, the therapeutic value of medial branch blocks has not been determined. This study was designed to evaluate the duration of relief obtained and therapeutic value following controlled medial branch blocks with or without adjuvant agents Sarapin (High Chemical Company, Levittown, PA) and Depo-medrol (Pharmacia and Upjohn Company, Kalamazoo, MI). The study population consisted of 180 consecutive patients seen in a single pain management practice, divided into three groups with 60 patients in each group. Group I was treated with local anesthetic only, Group II with the addition of Sarapin, and Group III with the addition of Depo-medrol along with Sarapin. The prevalence of facet joint pain in chronic low back pain was determined as 36%, with a false-positive rate of 25%. Comparison of duration of relief in days with each block in the three groups showed that the relief was significantly superior in Group III compared with Group I and Group II, whereas Group II was superior to Group I.

Interventional techniques in the management of chronic pain: Part 1.0.

The practice guidelines for interventional techniques in the management of chronic pain are systematically developed statements to assist practitioner and patient decisions about appropriate health care related to chronic pain. These guidelines are professionally derived recommendations for practices in the diagnosis and treatment of chronic or persistent pain. They were developed utilizing a combination of evidence and consensus to improve quality of care, increase patient access,improve patient outcomes, improve appropriateness of care, improve efficiency and effectiveness, and achieve cost containment. Included in the guidelines is a discussion of their purpose,rationale, importance, and methodology, and patient population, pathophysiologic basis, and various interventional techniques utilized in the management of chronic pain including rationale, outcomes, and cost effectiveness. They also describe the role of diagnostic blocks and therapeutic blocks with suggested algorithms for interventional techniques in the management of conservative care of chronic pain.

Percutaneous lysis of epidural adhesions.

Percutaneous epidural adhesiolysis, lysis of epidural adhesions, percutaneous neuroplasty, or epidural neurolysis is an interventional pain management technique which emerged during the latter part of the 1980s. It is becoming established as a common treatment modality in managing chronic low back pain that is nonresponsive to other modalities of treatment. While epidural adhesions most commonly result following surgical intervention of the spine, leakage of disc material into the epidural space following an annular tear, or an inflammatory response can also result in the formation of epidural adhesions. Even though advanced technology, including computerized tomography and magnetic resonance imaging, have made significant advances in the diagnosis of epidural fibrosis, it is believed that epidural adhesions are best diagnosed by performing an epidurogram. Percutaneous lysis of epidural scar tissue, followed by the injection of hypertonic saline neurolysis, has been shown to be cost effective in multiple studies. This review discusses various aspects of percutaneous nonendoscopic adhesiolysis and hypertonic saline neurolysis including clinical effectiveness, complications, rationale, and indications.

Non-endoscopic and endoscopic adhesiolysis in post-lumbar laminectomy syndrome: a one-year outcome study and cost effectiveness analysis.

Post lumbar laminectomy syndrome with its resultant chronic low back pain is estimated to occur in 20% to 50% of the patients. Among various procedures available, lysis of epidural adhesions is considered as one of the effective therapeutic modalities of management in these patients, and may be performed either non-endoscopically or endoscopically. This retrospective evaluation included 120 post lumbar laminectomy patients who underwent either non-endoscopic adhesiolysis (Group I) or endoscopic adhesiolysis (Group II) with 60 consecutive patients in each group. The quality of pain relief when greater than 50% was considered significant. Results showed all patients experienced significant relief following both procedures even though the number of patients experiencing significant relief decreased with both techniques over a time period. Overall relief with the first procedure (mean + SEM) was 12 + 3.2 weeks for Group I, and it was 20 + 2.9 weeks for Group II with significantly longer improvement in Group II than Group I. At one year follow up, the results showed that with repeat procedures, 72% in Group I and 40% in Group II experienced significant relief at 6 months, whereas at 12 months, it decreased to 52% in Group I and 22% in Group II, with a significantly greater number of patients experiencing relief at 6 months and 12 months in Group I, than Group II, even though Group I patients underwent a greater number of procedures. Cost effectiveness analysis showed Group I patients experiencing significant relief at a cost of $40 per week, with one year quality of life improvement for $2,080, whereas it was $135 per week improvement in Group II with a one year quality of life improvement at a cost of $7,020 with significant difference noted in cost effectiveness. In conclusion, non-endoscopic epidural adhesiolysis and administration of corticosteroids and hypertonic saline is a safe and cost effective procedure for relieving chronic intractable pain in post lumbar laminectomy patients who failed to respond to other modalities of treatment. Similarly, endoscopic adhesiolysis with the administration of corticosteroids is also a safe and possibly cost-effective technique for relief of chronic intractable pain failing to respond to other modalities of treatments.

Prevalence of lumbar facet joint pain in chronic low back pain.

This prospective study was designed to determine the prevalence of lumbar facet joint pain in a consecutive series of patients with chronic low back pain treated at an interventional, multidisciplinary private pain management practice utilizing double diagnostic blocks, to determine the prevalence of false positive rate of uncontrolled facet joint blocks, and to determine the relationship of clinical features of responders and non-responders to double diagnostic blocks. One hundred and twenty patients with low back pain with or without lower extremity pain were selected. The procedure consisted of diagnostic blocks using lidocaine and bupivacaine on separate occasions, usually two weeks apart. Each facet joint nerve was infiltrated with either 0.4 to 0.6 ml of 1% lidocaine (Xylocaine(R)) or 1% lidocaine (Xylocaine(R)) and 0.25% bupivacaine (Marcaine(R)). A definite response was defined as substantial with at least 75% relief of pain in the symptomatic area following local anesthetic block. Confirmatory blocks using bupivacaine 0.25% were performed at the same levels as the first injection if definite relief was obtained. The response to bupivacaine blocks which lasted longer than the lidocaine blocks was accepted as a positive response. All blocks were performed under fluoroscopic guidance. Eighty-one patients (67.5%) reported a definite response to lidocaine blocks. Confirmatory blocks with bupivacaine were performed in all 81 patients with 54 patients, i.e. 45% of total sample or 66.6% of lidocaine positive group reporting definite response with a false positive rate of 41%. Prevalence and relationship of pain referral pattern in patients with and without facet joint pain confirmed by double blocks showed no significant correlation. We found no relationship between the history, physical findings, age, gender, trauma, duration of pain, and diagnostic blocks. However, history of previous surgery showed a negative correlation as only 29% of the patients after previous surgery were positive in contrast to 51% of the nonsurgical population. The results of this study echo previous concerns of reliability of uncontrolled single blocks, history, and clinical features. This study demonstrated that the facet joint is a source of pain in 45% of the patients suffering with chronic low back pain in an interventional pain management setting in a private practice.

Removal of a torn Racz catheter from lumbar epidural space.

BACKGROUND AND OBJECTIVES: Epidural adhesiolysis, described by Racz et al. (1) utilizing a double-contrast injection technique, provides an epidurogram that clearly delineates the area of adhesions and furnishes a means to perform lesion-specific lysis of adhesions utilizing a flexible wire-embedded catheter. METHODS: A caudal/lumbar epidurogram followed by lysis of adhesions was attempted in a 68-year-old male suffering with severe, low back pain with radiation into both lower extremities, using R-K needle and the Racz catheter (Medic Epimed, Gloversville, NY) under fluoroscopic visualization. RESULTS: After the cannulation and during the attempts to manipulate, the Racz catheter was sheared and was retained in the epidural space. After unsuccessfully attempting to remove it endoscopically, it was successfully removed using arthroscopy forceps. CONCLUSIONS: This case report illustrates a difficult situation with a sheared and retained epidural catheter which could not be removed utilizing the standard techniques but was successfully removed without any residual problems using arthroscopy forceps.

Recovery of cholinergic phenotype in the injured rat neostriatum: roles for endogenous and exogenous nerve growth factor.

Polyclonal antibodies against recombinant human nerve growth factor (rhNGF) potently inhibited PC12 neurite outgrowth, blocked high-affinity 125I-rhNGF binding but not its receptor, and cross-reacted with rat, mouse, and human nerve growth factor (NGF) but not with brain-derived neurotrophic factor, neurotrophin-3, ciliary neurotrophic factor, insulin-like growth factor, epidermal growth factor, or activin A. Immunocytochemistry revealed many NGF-positive neurons in the rat neostriatum. The NGF-positive neurons disappeared by 3 days after mechanical injury to the neostriatum and were replaced by intensely NGF- and glial fibrillary acidic protein-positive astrocytes. Enzyme-linked immunosorbent assay measurements revealed that the NGF content of the injured striatum was elevated by eightfold 3 days postinjury and by twofold 2 weeks later. The high-affinity choline uptake (HACU) into cholinergic nerve terminals was decreased by 23% at 2 and 4 weeks postinjury, yet choline acetyltransferase (ChAT) activity in these neurons was unchanged at 2 weeks and decreased by 14% at 4 weeks. Daily infusion of 1 microgram of rhNGF into the injury area did not alter the loss of HACU. However, this treatment elevated ChAT activity by 23-29% above intact neostriatal levels and by 53-65% relative to HACU at both survival times. Thus, lesion-induced increases in NGF levels within astrocytes are associated with maintenance of striatal ChAT activity at normal levels following cholinergic injury, even with decreases in HACU. Pharmacologic doses of rhNGF can further augment ChAT activity in damaged cholinergic neurons, showing the usefulness of exogenous NGF even when endogenous NGF is elevated in response to injury.

Increase in glia-derived nerve growth factor following destruction of hippocampal neurons.

It is currently believed that under normal conditions hippocampal neurons synthesize nerve growth factor (NGF) which may provide trophic support for cholinergic neurons projecting from the basal forebrain. The concept that glial cells are mobilized to increase the production of NGF following destruction of hippocampal neurons was examined. Excitotoxin-induced destruction of the dorsal hippocampal neurons resulted in a massive and prolonged increase in NGF-like immunoreactivity (LI). Immunostaining for NGF-LI and the glial marker, glial fibrillary acidic protein (GFAP), revealed that the source of increased NGF-LI production following the lesion were reactive astrocytes. Thus, glial cells assume the role of providing trophic support following loss of target neurons.

Increase in nerve growth factor-like immunoreactivity and decrease in choline acetyltransferase following contusive spinal cord injury.

We have previously described a graded spinal cord injury model in the rat. Mild contusive injury results in an initially severe functional deficit that is attenuated over time to reveal the mild chronic deficits that characterize this injury. In this study, we have shown that mild contusive injury also results in a significant decrease in choline acetyltransferase (ChAT) activity during the first week after injury. At 1 week ChAT activity is maximally reduced at the site of the contusion and is also significantly lowered throughout the spinal cord. ChAT activity then rebounds during the following 3 weeks, partially at the injury site where there is considerable loss of gray and white matter, and completely in rostral and caudal cord segments. The rebound in ChAT activity is temporally associated with the partial recovery of function. Further, the changes in ChAT activity after injury are mirrored by changes in nerve growth factor-like immunoreactivity (NGF-LI) as determined by a specific two-site ELISA. NGF-LI increases significantly after injury, reaching a maximum at 7 days after contusion and at the injury site. However, levels of NGF-LI are also significantly increased throughout the spinal cord. NGF-LI then decreases at 2 and 4 weeks as ChAT activity rebounds. Further experiments will be needed to examine the possibility of a role for NGF in promoting the recovery of function after spinal cord injury.

Medial-to-lateral gradient of neostriatal NGF receptors: relationship to cholinergic neurons and NGF-like immunoreactivity.

High-affinity binding sites for recombinant human NGF (rhNGF) were studied in the caudate-putamen of the adult rat and rabbit. Displaceable 125I-rhNGF binding sites were densely distributed throughout the caudate-putamen and were 2-3-fold more prevalant in the ventrolateral and lateral than in the medial caudate-putamen. The amount of nondisplaceable binding did not vary throughout the caudate-putamen. The medial-to-lateral receptor gradient was correlated (r = +0.99) with a 2-3-fold medial-to-lateral increase in ChAT activity. In contrast, NGF-like immunoreactivity (NGF-LI) was prevalent but uniformly distributed in the caudate-putamen. Lesions of intrinsic cholinergic neurons by quinolinic acid produced extensive gliosis in the medial, central, and lateral caudate-putamen, yet 125I-rhNGF binding was decreased in each of these regions. The activity of ChAT and 125I-rhNGF binding throughout the caudate-putamen were each decreased by 40% following quinolinic acid. Binding was not changed after 70-77% dopamine nerve terminal depletions induced by 6-hydroxydopamine, demonstrating a nonglial, nondopaminergic locus for striatal NGF binding sites. The cholinergiclike topography of NGF binding sites throughout the intact caudate-putamen, the parallel decreases of cholinergic neurons and NGF binding sites following intrinsic neuronal loss, and the uniform neostriatal gradient of NGF-LI are consistent with the trophic role of endogenous NGF for cholinergic interneurons of the caudate-putamen.

Receptor-mediated transport of human recombinant nerve growth factor from olfactory bulb to forebrain cholinergic nuclei.

Receptors for nerve growth factor are present in the olfactory bulb and in cholinergic nuclei that send projections to the olfactory bulb. The retrograde transport of 125I-labeled recombinant human nerve growth factor (rhNGF) was demonstrated in the rat 18 h following an injection of [125I]rhNGF into the left olfactory bulb. In each of six animals, [125I]rhNGF label was observed in the ipsilateral horizontal limb of the diagonal band and, in four of the 6 animals, in the vertical limb of the diagonal band. Label was not observed in any other brain region except within the injected olfactory bulb. The transport of label to the diagonal band was blocked by the injection of 170-fold greater concentration of unlabeled rhNGF. Emulsion autoradiography of hematoxylin/eosin counterstained sections revealed silver grains clustered over numerous cell profiles that resembled neurons. In contrast, cerebellar injections of [125I]rhNGF, with or without unlabeled rhNGF, did not label diagonal band neurons, nor the lateral vestibular or red nuclei, from which originate the primary cholinergic afferents to cerebellum. The receptor-dependent transport of NGF from olfactory bulb to forebrain cholinergic nuclei suggests that this projection, unlike pontomesencephalic cholinergic pathways, may be responsive to endogenous NGF or exogenously administered rhNGF.

The pharmacokinetics and pharmacodynamics of a human relaxin in the mouse pubic symphysis bioassay.

The effects of dose, route, regimen, and the presence or absence of a repository vehicle [benzopurpurine (BPP)] were determined for a human relaxin (hRlx) in the mouse pubic symphysis bioassay. Administration of 88 micrograms/kg hRlx sc in 1% BPP resulted in delayed, prolonged absorption. Although peak hRlx concentrations were lower, serum concentrations remained elevated longer in the presence of BPP compared to a single sc administration of hRlx in saline at the same dose. The bioavailabilities with and without BPP were similar (109 and 96%, respectively). While the pharmacodynamic effect (i.e. lengthening of the pubic ligament in estrogen-primed mice) was approximately maximum at 88 micrograms/kg hRlx sc with BPP, single sc administration of hRlx without BPP up to 264 micrograms/kg had no effect on pubic ligament length. In the absence of the BPP vehicle, manipulation of the regimen (e.g. multiple sc doses) showed that emulation of the serum concentration-time profile observed for hRlx in the presence of BPP resulted in similar pharmacodynamic effects. It appears that BPP delays the absorption of hRlx after sc administration, resulting in prolonged, elevated hRlx serum concentrations. hRlx has been shown to be effective in this model without BPP if it is administered by a multidose sc schedule. As has been observed with other protein therapeutics, the dosage regimen employed for hRlx delivery appears to be an important determinant of the expression of its pharmacodynamic effects.

Decreased locomotor activity produced by repeated, but not single, administration of murine-recombinant interferon-gamma in mice.

A single treatment with murine-recombinant interferon-gamma (murIFN-gamma; 30 micrograms/mouse), whether evaluated immediately after, or four hrs after, intraperitoneal injection, does not alter open field activity levels. On the other hand, repeated murIFN-gamma administration (30 micrograms/mouse/day for 5 days) results in decreased spontaneous locomotor activity and an increase in body weight.

Human relaxin increases cyclic AMP levels in cultured anterior pituitary cells.

Although relaxin acts at several abdominal sites and mammary tissue associated with pregnancy and parturition, the scope of target tissues and the signals conveying the relaxin message into the cell are poorly defined. We found that human relaxin rapidly elevates the cyclic AMP content of cultured rat anterior pituitary cells. This is a graded response (EC50 0.3 nM relaxin) that can be blocked by anti-relaxin antibodies or the hormones somatostatin and dopamine. Furthermore, other hormones with some sequence homology to relaxin, such as insulin and insulin-like growth factor-I, have no such action. We conclude that the anterior pituitary may be a target tissue for relaxin and that cyclic AMP may act as an intracellular messenger for relaxin in these cells.

Cellular catabolism of recombinant tissue-type plasminogen activator. Identification and characterization of a novel high affinity uptake system on rat hepatocytes.

The uptake, internalization, and intracellular degradation of 125I-labeled recombinant tissue-type plasminogen activator (rt-PA) by isolated rat hepatocytes was investigated. Incubation at 37 degrees C resulted in internalization of 125I-rt-PA, followed by the appearance of labeled trichloroacetic acid-soluble material in the incubation media due to degradation of rt-PA. Degradation of rt-PA was inhibited by the presence of NH4Cl (10 mM) or chloroquine (1 mM) (lysosomal tropic agents) in the incubation media. This suggests that rt-PA degradation occurs intracellularly, perhaps within the lysosomes. 125I-rt-PA was taken up by rat hepatocytes through a specific, high affinity mechanism with half-maximal uptake at 10 nM. Uptake of 125I-rt-PA was not inhibited by glycopeptides isolated from rt-PA nor by several other glycoproteins known to be cleared by identified hepatic receptors. These results suggest that the uptake of rt-PA by rat hepatocytes involves a receptor specific for t-PA and is not mediated by a carbohydrate-specific receptor.

Behavioral changes following central injection of cysteamine in rats.

When tested 3 days following 4 daily intracerebroventricular injections of 250 micrograms cysteamine, which depletes somatostatin, rats demonstrated a significant increase in locomotor activity that was not observed in animals treated similarly with 350 micrograms cysteamine. A significant deficit in passive avoidance was observed in animals treated with the 350-micrograms dose, but not in animals treated with 250 micrograms cysteamine. These data suggest that altered activity of the somatostatinergic system disrupts specific processes underlying neural integration of complex behaviors.

Brain-specific gene expression.

The brain of an adult rat expresses approximately 30,000 different brain-specific mRNAs. To investigate their encoded proteins, we have selected cDNA clones corresponding to mRNAs expressed exclusively in rat brain, determined their nucleotide sequences and generated antisera against synthetic peptides mimicking short regions of the deduced protein sequences. The clone plB236 encodes a protein that defines a widely distributed neuronal system and may be the precursor for a family of novel neuropeptides. A second clone, plB208, encodes rat brain proteolipid protein, the major protein component of central nervous system myelin. These studies have also identified an 82 nucleotide genetic element called an ID (identifier) sequence that may be involved in the regulation of transcription of brain-specific genes.