Biomedical subjects
Publications and source records attributed to Marco Pappagallo.
We describe a case of atypical primary headache strongly responsive to prolonged pressure in the anterior aspect of the neck. We hypothesize that, at least in this case, the trigemino-cervical system and its connections with the vagus nerve are involved.
Chronic pain, whether arising from viscera, bone, or any other tissue or structure, is, more often than commonly thought, the result of a mixture of pain mechanisms, and therefore there is no simple formula available to manage chronic complex pain states. Box 1 summarizes a pharmacological algorithm for difficult-to-treat chronic pain, which merely introduces the medication aspect of the treatment. In effect, any comprehensive algorithm should call for an interdisciplinary approach that would include rehabilitation, as well as psychosocial, and when indicated, interventional techniques. Box 1 Analgesic algorithm for difficult-to-treat pain syndromes. Pharmacological Interventions. Moderate to severe pain/functional impairment; pain with a score of >4 on the brief pain inventory. 1. Gabapentinoid (gabapentin, pregabalin)+/-Opioid/opioid rotation or 2. Antidepressant (TCA, duloxetine, venlafaxine)+/-Opioid/opioid rotation or 3. Gabapentinoid+antidepressant+Opioid/opioid rotation; in addition, may consider trials of one or more of the following adjuvants when clinically appropriate: Topical therapies for cutaneous allodynia/hyperalgesia. Anti-inflammatory drugs (corticosteroids for acute inflammatory neuropathic pain)IV bisphosphonates for cancer bone pain or CRPS/RSDNon-gabapentinoid AEDs such as carbamazepine or oxcarbazepine or lamotrigine+/-baclofen for intermittent lancinating pain due to cranial neuralgiasNMDA antagonists Mexiletine On a compassionate basis, according to the patient's clinical condition and pain mechanism, the physician may want to consider an empirical trial of one or more of the emergent topical, oral or parenteral/intrathecal therapies as discussed in the text. If SMP, consider topical clonidine and sympatholytic interventions; if clinically feasible, trials of topical therapies, eg, lidocaine 5% patch, may be considered for a variety of pain states and features.The major rationale for introducing adjuvants is to better balance efficacy and adverse effects. The following scenarios should prompt the use of adjuvants in clinical practice: The toxic limit of a primary analgesic has been reached. The therapeutic benefit of a primary analgesic has plateaued, eg, treatment has reached its true efficacy limit or pharmachodynamic tolerance has developed. The primary analgesic is contraindicated, eg, substance abuse, aberrant behavior, organ failure, allergy, and so forth. Subjective and qualitative symptoms demand broader coverage. Patients often convey that different medications will impart distinct analgesic benefits. Presence of disabling nonpainful complaints and need to manage symptoms such as insomnia, depression, anxiety, and fatigue that all cause worsening of the patient's quality of life and function. Physicians have also been drawn to the adjuvants secondary to new realities of clinical practice. Moreover, aversion to addiction and diversion remains a potent force that shapes prescribing profiles.
UNLABELLED: We determined the profiles of the board-certified pain physician workforce and the profiles of those residing near medical pain practices. Data from a mail survey of U.S. pain specialists were compared with U.S. Census data, and different settings and types of practices were contrasted. The 750 respondents (32.1%) were similar to the entire board-certified group in age, geographic distribution, and primary specialty. Although pain practices were underrepresented in rural areas, their prevalence was unrelated to other demographic data. Ninety-six percent of pain physicians treated chronic pain; 84% followed patients longitudinally; 31% worked in an academic environment; 50% had an interdisciplinary practice; and 29% focused on a single modality. Academics were more likely to be neurologists (P < .05) and to have had a pain fellowship (P < or = .0001). Modality-oriented practitioners were more likely to be anesthesiologists (P < or = .0001) and were less likely to follow patients with chronic pain longitudinally (P < or = .0001), provide training to fellows, prescribe controlled substances (P < or = .0001, respectively), or require an opioid contract (P < or = .01). Although boarded specialists learn from similar curricula and must pass a certifying examination, their practices vary considerably. Data are needed to further clarify the nature of workforce variation, its impact on patient care, and the role of other pain management clinicians. PERSPECTIVE: A survey of board-certified pain specialists reveals considerable variation in practice and a total number of specialists that is probably insufficient to meet the needs of the population with chronic pain. The location of pain management practices largely corresponds to census data, with the exception of underrepresentation in rural areas.
OBJECT: Morphine-based compounds are used epidurally after lumbar microdiscectomy to minimize postoperative pain. After the withdrawal of ADCON-L we started to use Oxiplex (Oxiplex/SP Gel) as a barrier against epidural fibrosis and as a vehicle for morphine delivery. METHODS: We administered epidurally morphine (1 mg) dissolved in Oxiplex gel to 20 consecutive patients after lumbar microdiscectomy, evaluating safety and analgesic effectiveness. Outcome measures adopted were (1) visual analog scale (VAS) of back and radicular pain, (2) straight leg raising (SLR) maneuver to assess evoked pain, (3) postoperative time to comfortable ambulation, (4) postoperative hospitalization, (5) postoperative request of analgesics, and (6) postoperative work time loss. RESULTS: No complications, such as urinary retention, respiratory disturbances, or wound infections, were observed. During the first 24 hours the mean VAS was lower than the preoperative one (12.5 vs 77.3 mm, respectively; P < .01). The mean postoperative SLR was 62.25 degrees vs 38.74 degrees of preoperative period (P < .05). After a mean of 29.8 hours, patients were discharged. Twelve patients (60%) had low back and radicular pain relapse 36 to 72 hours after operation, requiring assumption of analgesics. At that time, 2 patients reported a level of pain higher than the preoperative one. At 1- and 2-week follow-up visits, mean VAS scores were 33.5 and 12.0 mm, respectively. The 2-week overall treatment satisfaction rating was excellent for 60% and good for 40%. Finally, the mean postoperative work time loss was 27 days. CONCLUSIONS: The epidural application of Oxiplex-morphine compound after lumbar microdiscectomy was found to be safe. Regarding postoperative pain control, it was found to be effective only during the first 36 hours.
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Post-herpetic neuralgia (PHN) is a neuropathic pain state that is often difficult to treat. Although frequently discussed in the clinical literature, little is known about the impact of pain on daily function and the extent to which psychosocial factors, in particular pain coping strategies, influence adaptation to this chronic illness. In the context of a crossover pharmacological trial, 68 patients with PHN completed a battery of psychological measures during a first drug-free baseline period. Following discontinuation of approximately 8 weeks of treatment, 49 of these patients completed data collection during a second drug-free assessment prior to beginning a second drug phase. Twice-weekly telephone pain ratings were combined with questionnaire measures of perceived interference due to pain, overall activity level, depressive symptoms, and pain coping strategies. Cross-sectional hierarchical regression analyses indicated that catastrophizing correlated with depressive symptoms but not pain, and coping self-statements were correlated with higher levels of overall activity. Prospective hierarchical regression analyses indicated that catastrophizing at baseline predicted level of pain 8 weeks later, an effect that was independent of baseline pain and depressive symptoms. Patients who reported increasing their activity in response to pain also reported more perceived interference due to pain 8 weeks later. Higher levels of ignoring pain sensations at baseline were prospectively correlated with more depressive symptoms 8 weeks later. These findings support a role for the continued investigation of cognitive-behavioral factors affecting the adaptation of elderly individuals experiencing PHN.
BACKGROUND: Both neuropathic pain and migraine are now being treated with a variety of newer antiepileptic drugs (AEDs). The proven efficacy of gabapentin in postherpetic neuralgia (PHN) and painful diabetic neuropathy (PDN), and of divalproex sodium in the prevention of migraine has led to increased clinical investigation of the newer AEDs for these conditions. While basic and clinical research are expanding the knowledge base concerning the fundamental mechanisms of neuropathic pain and migraine, growing recognition of the similarities in the pathophysiology of epilepsy, migraine, and various chronic pain disorders has further heightened interest in exploring the newer AEDs in the treatment of these conditions. OBJECTIVE: The goals of this article were to review the empiric basis and scientific rationale for the use of AEDs in the treatment of neuropathic pain and migraine; summarize available clinical research on the use of 5 newer AEDs (gabapentin, lamotrigine, oxcarbazepine, topiramate, and zonisamide) in these conditions; and provide a summary comparison of the dosing, tolerability, and drug-interaction potential of these agents. METHODS: Relevant English-language articles were identified through searches of MEDLINE (1990-March 2003), American Academy of Neurology abstracts (1999-2003), and American Epilepsy Society abstracts (2000-2002). The search terms were antiepileptic medication or drug, migraine headache, neuropathic pain, pathophysiology, treatment, mechanism of action, gabapentin, lamotrigine, oxcarbazepine, topiramate, and zonisamide. CONCLUSIONS: The newer AEDs possess the potential advantages of better tolerability and fewer drug-drug interactions compared with standard treatments such as tricyclic antidepressants or established AEDs. However, with the exception of data supporting the efficacy of gabapentin in PHS and PDN, there is currently insufficient evidence to determine whether the newer AEDs have equal or superior efficacy relative to proven pharmacotherapies.
We explored the effect of intravenous infusions of a bisphosphonate, pamidronate, in the management of chronic mechanical spinal pain, a worldwide public health problem in terms of lost workdays, medical treatment costs, and suffering. Bisphosphonates have an anti-nociceptive effect in animals. In humans, intravenous pamidronate relieves numerous painful conditions, including metastatic bone pain, ankylosing spondylitis, rheumatoid arthritis, and complex regional pain syndrome. We reviewed the charts of 25 patients who had experienced disabling spinal pain for several years, and whom we treated with intravenous pamidronate. None had a history of osteoporotic vertebral fractures or metastatic disease. Pain rating scores decreased in 91% of patients: on a 0-10 numeric rating scale, the mean pain change was -3.6 points and mean percentage change was -41% (P<0.0001). There was no increase in opioid or nonopioid analgesic medications associated with pain relief. The apparent analgesic effect of pamidronate for chronic mechanical spinal pain needs to be confirmed with placebo-controlled trials.
Postherpetic neuralgia, which occurs most typically in older persons, is one of the most common and serious complications of herpes zoster (or shingles). It is a chronic neuropathic pain syndrome and remains one of the most difficult pain disorders to treat. Known beneficial agents include antidepressants, antiepileptic drugs, opioid analgesics, local anaesthetics, capsaicin and other, less applied, modalities. Although monotherapy is commonly applied, no single best treatment for postherpetic neuralgia has been identified; nevertheless, gabapentin (antiepileptic) and transdermal lidocaine (anaesthetic) are often used as the first-choice treatments. Recent research has shed light on possible pain mechanisms as well as new avenues of treatment, which are discussed in the article. For patients with pain that is not adequately controlled, individualised treatment plans must be pursued. It is critical to recognise that postherpetic neuralgia, while difficult to manage, can be a treatable neuropathic pain syndrome.
OBJECTIVE: Epidural analgesia is a pharmacological technique for operative and postoperative pain control. It has been used with lumbar microdiscectomy to facilitate management of surgical pain, shorten patient recovery time, and increase patient satisfaction with the procedure and the hospital stay. Adcon-L (Gliatech, Inc., Cleveland, OH) (adhesion control in a barrier gel) has been demonstrated to act as a barrier to the development of epidural fibrosis after lumbar procedures, minimizing the formation of fibrotic scar and improving the long-term outcome. In this study, we used Adcon-L as a vehicle to administer 1 mg of morphine epidurally to patients who underwent lumbar microdiscectomy. Our objective was to evaluate the safety and analgesic efficacy of this compound. METHODS: A randomized, controlled, double-blind study was conducted in 100 patients. Patients were randomized to two groups: the morphine-Adcon-L (M-ADL) group (n = 51 patients) or the Adcon-L control group (n = 49 patients). Outcome measures included: 1) a visual analog scale to assess the intensity of spontaneous low back and radicular pain, 2) a straight leg-raising maneuver to assess the degree of leg elevation in relation to evoked sciatic pain, 3) postoperative time to comfortable walking, 4) duration of postoperative hospitalization, 5) required amount of postoperative analgesics, and 6) postoperative work time loss. RESULTS: No intraoperative or postoperative complications were observed. No clinically relevant adverse events, such as urinary retention, respiratory disturbances, or wound infections were reported in the M-ADL group. At the time of hospital discharge, results were as follows: 1) the M-ADL group had significantly lower pain intensity scores (mean value of postoperative visual analog scale, 12.3 mm +/- 0.9 in the M-ADL group versus 24.7 mm +/- 11.5 in the control group[P < 0.0001]); 2) the M-ADL group consumed significantly less analgesics: 57.4% of M-ADL patients versus 95.9% of controls received analgesics in the hospital, and 23.5% of M-ADL patients versus 55.1% of controls used analgesics at home (P < 0.0001); 3) the M-ADL group had significantly shorter hospital stays (1.37 +/- 0.07 d versus 2.53 +/- 0.12 d in the control group[P < 0.0001]); 4) the M-ADL group had a significantly higher degree of symptomatic leg elevation in the straight leg raising (mean postoperative straight leg-raising test, 64.41 degrees +/- 1.59 versus 57.77 degrees +/- 1.85 in the controls[P = 0.02]); and 5) the M-ADL group lost significantly less postoperative work time (21.67 +/- 0.92 d versus 29.47 +/- 1.18 d in the control group). In addition, at 1 year of follow-up, there was no clinical evidence of late-onset neurological complications. CONCLUSION: The epidural application of the compound M-ADL after lumbar microdiscectomy was found to be safe and effective, and it significantly improved postoperative pain control and return to function.
Topical capsaicin has been reported to be beneficial for the treatment of neurogenic pain. However, due to the burning pain associated with topical capsaicin, many patients discontinue treatment before therapeutic benefits are obtained. This study assessed the efficacy of EMLA (eutectic mixture of 2.5% prilocaine and 2.5% lidocaine) to block pain induced by the topical application of 1% capsaicin. Nine healthy subjects (five males and four females) participated in the study. High dose topical capsaicin (1%) was applied to a 2.5 x 2.5 cm region of both volar forearms for 6 h. One arm was pretreated (for 2 h) and cotreated with EMLA, and the other arm served as vehicle control. Average and peak pain ratings were recorded at 15-min intervals using a 0 (no pain) to 10 (worst possible pain) scale. Average and peak pain ratings were significantly lower at the EMLA site during the first 15-30 min of capsaicin treatment. However, for the remaining 5.5 h of capsaicin treatment, the pain ratings at the EMLA and vehicle sites were not significantly different. The 6 h treatment with high dose topical capsaicin (1%) produced significant desensitization to heat stimuli that was not affected by EMLA treatment. EMLA fails to produce a long lasting attenuation of the pain induced by topical application of 1% capsaicin. These results argue against the use of EMLA to block pain to topical capsaicin during the treatment of neurogenic pain.
Intradermal injection of the capsaicin analogue, NE-21610 (Procter and Gamble), inactivates nociceptors but not low-threshold mechanoreceptors in monkey. The present study examined the effects of cutaneous NE-21610 on heat and mechanical sensation in normal human volunteers. In the first series of experiments, subjects received intradermal (i.d.) injections (30 microliters) of the vehicle alone or with the drug (0.3, 3.0, 10 micrograms) into different sites on the volar forearm. Subjects were randomly assigned to 1 of 3 protocols to examine drug-evoked pain (n = 8), or alterations in pain to heat (n = 8) or mechanical (n = 8) stimuli induced by the drug. An additional 7 subjects rated pain to mechanical and heat stimuli before and after subcutaneous (s.c.) injections (300 microliters) of the vehicle or drug (100 micrograms). The peak pain occurred at the time of injection, was of short duration, and was similar for vehicle and drug injections. A mild, dose-related pain followed that lasted up to 2 h. Von Frey thresholds for detection, sharpness, and pain at the injection site (measured 24 h after injection) were not significantly altered by either i.d. or s.c. drug administration. However, pain to stepped heat stimuli was reduced in a dose-dependent fashion for both types of injection. At the highest drug doses, analgesia to heat stimuli was still present 1 week after injection. Recovery of heat sensitivity occurred several weeks after injection. This dissociated loss of heat but not mechanical pain sensibility may be due to: (1) a selective action of the drug on heat transducers in nociceptors responsive to both heat and mechanical stimuli, or (2) a selective action on that subset of nociceptors responsible for signaling heat-evoked pain.
Cutaneous injection of the capsaicin analog NE-21610 (Procter and Gamble) produces analgesia to heat but not mechanical stimuli in humans. The present study examined whether pretreatment of the skin with NE-21610 prevents the development of hyperalgesia following heat injury. On the 1st day testing, 7 volunteers received a 30-microl intradermal injection of vehicle to one volar forearm and 10 micrograms of NE-21610 to the other volar forearm. On the 2nd test day the subjects rated the intensity of pain to mechanical and heat stimuli before and after a burn (48 degrees C, 120 sec) to each injection site. At the vehicle site, the pain evoked by the burn was rated as moderate to strong. In addition, primary hyperalgesia to heat and mechanical stimuli, secondary hyperalgesia to mechanical stimuli, and flare were observed after the burn. In contrast, the pain evoked by the burn at the NE-21610-treated site was rated as weak, and primary hyperalgesia to heat and mechanical stimuli did not develop. In addition, the area of flare at the drug-tested site was smaller than that observed at the vehicle site, and no secondary hyperalgesia to mechanical stimuli was observed. These data suggest that pretreatment with the capsaicin analog NE-21610 may attenuate the pain and hyperalgesia associated with injury.
Adenosine is known to cause pain when injected intravenously or intra-arterially. We have conducted a double-blind placebo-controlled study by injecting adenosine intradermally in 6 healthy subjects (5 male, 1 female; age: 27-34 years). Pain was assessed using the visual analogue scale. The intradermal injection of 2 mumol of adenosine produced pain significantly greater than normal saline after 15 sec (T0) (29 +/- 13 vs. 7 +/- 6 mm, P = 0.004), 1 min after T0 (13 +/- 9 vs. 0 +/- 0 mm, P = 0.002) and 2 min after T0 (4.5 +/- 5 vs. 0 +/- 0 mm, P < 0.05). There was evidence of hyperalgesia to mechanical and heat stimuli at the injection site (primary hyperalgesia). There was no evidence of mechanical hyperalgesia in the cutaneous area surrounding the injected site (secondary hyperalgesia). In all cases the intradermal injection of adenosine produced local hyperemia (mean surface are: 147 +/- 69 mm2) which was absent after placebo injection. The pre-injection of bamiphylline, a rather selective antagonist of A1 adenosine receptors, differently from placebo, completely suppressed the adenosine-induced pain after 15 sec (T0) (15 +/- 10 vs. 0 +/- 0 mm, P = 0.002) and 1 min after T0 (9 +/- 7 vs. 0 +/- 0 mm, P = 0.002). No anesthesia to heat, cold and mechanical stimuli was detected at the bamiphylline site. The adenosine-induced erythematous area was wider at the bamiphylline pre-injected site than at the placebo pre-injected site (173 +/- 114 vs. 119 +/- 85 mm2).(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: We conducted a pilot trial to assess the effect of botulinum toxin B on palmar pain and discomfort in carpal tunnel syndrome (CTS) patients. Design. Randomized, double-blind, placebo-controlled. PATIENTS: Twenty ambulatory CTS patients. Intervention. Botulinum toxin B or placebo injections into three hypothenar muscles anatomically linked or attached to the carpal tunnel and its tentorium, that is, the Opponens Digiti Minimi and Flexor Digiti Minimi, located with electromyography (EMG), and the Palmaris Brevis Muscle, anatomically located without EMG. SETTING: New York City hospital. OUTCOME MEASURES: Outcomes were measured with numeric ratings, with higher scores indicating worse outcomes. Daily, subjects recorded their 0-10 numeric ratings of overall pain levels and pain-related sleep disturbances. During weekly telephone calls, they reported their 0-10 ratings for overall pain, pain-related sleep disturbance, and CTS-related tingling during the night and day as experienced over the preceding 24 hours. For each of four clinic visits, we averaged each subject's ratings of nine quality of life indicators from the West Haven-Yale Multidimensional Pain Inventory (WHYMPI), each measured on a 0-6 numeric scale. RESULTS: Over the 13-week trial, compared to baseline scores, the following outcomes predominantly showed decreases of statistical significance (P < or = 0.050) or borderline significance (0.050 < P < or = 0.10) for weeks 2 through 8: overall pain per daily diary entries and per weekly telephone reports, and pain-related sleep disturbance in the placebo group per phone report and in the botulinum toxin B group per diary report. CTS painful night tingling and day tingling, as well as the average scores of the WHYMPI quality of life indicators, showed improvements with statistical or borderline significance for almost each follow-up week. Between-group analyses, however, demonstrated that at each follow-up week, there was no statistically significant difference between the two study groups regarding changes from baseline in any study outcome. CONCLUSION: Botulinum toxin B is not dramatically superior to placebo for the relief of CTS symptoms. Possible explanations of the improvements in each study group are explored.