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Neuropathic pain in leprosy: symptom profile characterization and comparison with neuropathic pain of other etiologies

imageIntroduction:
Previous studies reported a high prevalence of neuropathic pain in leprosy, being especially present in “pharmacologically cured” patients. The presence of neuropathic pain in leprosy poses a supplementary burden in patient’s quality of life, daily activities, and mood.
Objectives:
The aim of this study was to assess whether neuropathic pain in leprosy has similar symptom profile as neuropathic pain of other etiologies and to retrospectively assess the efficacy of neuropathic pain medications regularly prescribed to leprosy.
Methods:
Leprosy and nonleprosy patients had their neuropathic pain characterized by the neuropathic pain symptom inventory (NPSI, ranges from 0 to 100, with 100 being the maximal neuropathic pain intensity) in a first visit. In a second visit, leprosy patients who had significant pain and received pharmacological treatment in the first evaluation were reassessed (NPSI) and had their pain profile and treatment response further characterized, including information on drugs prescribed for neuropathic pain and their respective pain relief.
Results:
The pain characteristics based on NPSI did not significantly differ between leprosy and nonleprosy neuropathic pain patients in visit 1 after correction for multiple analyses, and cluster analyses confirmed these findings (ie, no discrimination between leprosy and nonleprosy groups; Pearson χ2 = 0.072, P = 0.788). The assessment of pain relief response and the drugs taken by each patient, linear regression analysis showed that amitriptyline, when effective, had the highest percentage of analgesic relief.
Conclusions:
Neuropathic pain in leprosy is as heterogeneous as neuropathic pain of other etiologies, further supporting the concept that neuropathic pain is a transetiological entity. Neuropathic pain in leprosy may respond to drugs usually used to control pain of neuropathic profile in general, and amitriptiline may constitute a potential candidate drug for future formal clinical trials aimed at controlling neuropathic pain in leprosy.

Neuropathic pain in leprosy: symptom profile characterization and comparison with neuropathic pain of other etiologies


Orginally Published At: PAIN Reports

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Capsaicin 8% patch reversibly reduces A-delta fiber evoked potential amplitudes

imageIntroduction:
The capsaicin 8% patch is a treatment option in patients with localized peripheral neuropathic pain. Better understanding of its mechanisms of action and knowledge on predictive biomarkers for a treatment response is warranted.
Objectives:
To use electrically evoked pain-related potentials for investigation of A-delta fiber conduction after capsaicin 8% patch treatment.
Methods:
We studied 11 healthy controls at the dorsal hand and the foot and 12 patients with neuropathic pain at the area affected by neuropathic pain before and 2 hours after application of a capsaicin 8% patch (Qutenza). Patients were additionally phenotyped using quantitative sensory testing and skin biopsy.
Results:
Peak-to-peak N1-P1 amplitudes (PPA) were reduced after Qutenza application by a median of 60% in 6/11 controls and by 33% in patients with neuropathic pain compared with baseline; they were increased in 3 controls that did not develop capsaicin-induced pain. Patients with elevated cold detection thresholds more often had reduced PPA after Qutenza than those with normal cold detection threshold. Patients with reduced PPA after capsaicin application and with capsaicin-induced pain were more likely to achieve pain reduction on Qutenza.
Conclusion:
The capsaicin 8% patch induces a reduction in A-delta PPA in healthy persons and in patients with neuropathic pain adding to the mechanistic understanding of its effect.

Capsaicin 8% patch reversibly reduces A-delta fiber evoked potential amplitudes


Orginally Published At: PAIN Reports

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Sensory symptom profiles differ between trigeminal and thoracolumbar postherpetic neuralgia

imageIntroduction:
Animal experimental evidence suggests that mechanisms of pain generation and response to treatment differ between neuropathic pain in the cephalic and the extracephalic innervation territories.
Objectives:
The objective of the study was to examine whether in humans an identical peripheral painful neuropathy is associated with different pain qualities and sensory abnormalities in the face as compared with the thoracic region.
Methods:
We retrospectively analysed epidemiological and clinical data of 639 patients with postherpetic neuralgia (PHN) in the face and at the trunk who were collected within a cross-sectional cohort survey and compared the respective sensory symptom profiles captured with the painDETECT questionnaire.
Results:
Two hundred twenty-four patients suffered from trigeminal PHN and 415 from thoracolumbar PHN. There were no significant differences in sex-ratio, age, body mass index, and pain duration. Patients with trigeminal PHN were more often severely depressed. Anxiety and sleep scores were not different. The average pain intensity was slightly higher in thoracolumbar PHN than trigeminal PHN (visual analogue scale 5.0 vs 4.6). Postherpetic neuralgia in the thoracolumbar region showed significantly more intense burning sensations, allodynia, painful attacks, and significantly less prickling and numbness than PHN in the face.
Conclusions:
The differences in sensory symptom profiles between facial PHN and truncal PHN might be associated with different pathophysiological mechanisms and different treatment response. Drugs that primarily act on sensitization processes in the peripheral nociceptive system may work better in thoracolumbar PHN than in trigeminal PHN. If new medications are tested in patients with PHN, it would therefore be of interest to include an analysis of the treatment results in regard to subgroups based on the localisation of pain in patients with PHN.

Sensory symptom profiles differ between trigeminal and thoracolumbar postherpetic neuralgia


Orginally Published At: PAIN Reports

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Specific symptoms may discriminate between fibromyalgia patients with vs without objective test evidence of small-fiber polyneuropathy

imageIntroduction:
Multiple studies now confirm that ∼40% of patients with fibromyalgia syndrome meet diagnostic criteria for small-fiber polyneuropathy (SFPN) and have objective pathologic or physiologic evidence of SFPN, whereas 60% do not. Given possibilities that tens or hundreds of millions globally could have SFPN, developing screening tools becomes important.
Objectives:
This analysis explored whether specific symptoms might help distinguish these fibromyalgia endophenotypes.
Methods:
With institutional review board approval, all adults tested for SFPN by distal-leg skin biopsy or autonomic function testing at Massachusetts General Hospital in 2014 to 2015 were queried about symptoms. Inclusion required a physician’s fibromyalgia syndrome diagnosis plus meeting the American College of Rheumatology 2010 Fibromyalgia Criteria. The primary outcome was the validated Small-fiber Symptom Survey, which captures severity of all known SFPN-associated symptoms. The Composite Autonomic Symptom Score-31, Short-Form Health Survey-36, and Short-Form McGill Pain Questionnaires provided secondary outcomes.
Results:
Among the 39 participants, 14 had test-confirmed SFPN (SFPN+) and 25 did not (SFPN−). Their pain severity did not differ. Paresthesias (“tingling”) were different (worse) in the SFPN+ group (3.14 ± 0.9 vs 2.28 ± 1.1; P = 0.16). Their component subscore for dysautonomia symptoms was also worse (10.42 ± 4.0 vs 7.16 ± 4.0; P = 0.019). Receiver operating characteristic analyses revealed that each item had fair diagnostic utility in predicting SFPN, with areas under the curve of 0.729. No secondary questionnaires discriminated significantly.
Conclusion:
Among patients with fibromyalgia, most symptoms overlap between those with or without confirmed SFPN. Symptoms of dysautonomia and paresthesias may help predict underlying SFPN. The reason to screen for SFPN is because—unlike fibromyalgia—its medical causes can sometimes be identified and definitively treated or cured.

Specific symptoms may discriminate between fibromyalgia patients with vs without objective test evidence of small-fiber polyneuropathy


Orginally Published At: PAIN Reports

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Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: an in vivo electrophysiological study

imageAbstractIntroduction:Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models.Objectives:In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL).Methods:In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain.Results:Tx3-3 (0.3–100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Aδ-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy.Conclusion:Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.
Introduction:
Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models.
Objectives:
In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL).
Methods:
In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain.
Results:
Tx3-3 (0.3–100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Aδ-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy.
Conclusion:
Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.

Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: an in vivo electrophysiological study


Orginally Published At: PAIN Reports

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Efficient conditioned pain modulation despite pain persistence in painful diabetic neuropathy

imageIntroduction:
Alleviation of pain, by either medical or surgical therapy, is accompanied by transition from less efficient, or pro-nociceptive, to efficient conditioned pain modulation (CPM). Spontaneous decrease or resolution of pain with disease progression is reported for some patients with painful diabetic neuropathy (PDN).
Objectives:
To explore whether CPM changes similarly in parallel to spontaneous resolution of pain in PDN patients.
Methods:
In this cross-sectional study, thirty-three patients with PDN underwent psychophysical assessment of pain modulation on the forearm, remote from the clinical pain.
Results:
Pain duration was not correlated with neuropathic pain intensity, yet, it correlated with CPM efficiency; patients with longer pain duration had same pain level, but more efficient CPM than those with short-pain duration (ρ = −0.417; P = 0.025, Spearman correlation). Patients with pain more than 2 years (median split) expressed efficient CPM that was not different from that of healthy controls. These patients also had lower temporal summation of pain than the short-pain duration patients group (P < 0.05). The 2 patient groups did not differ in clinical pain characteristics or use of analgesics.
Conclusion:
Pro-nociception, expressed by less efficient CPM and high temporal summation that usually accompanies clinical painful conditions, seems to “normalize” with chronicity of the pain syndrome. This is despite continuing pain, suggesting that pro-nociceptivity in pain syndromes is multifactorial. Because the pain modulation profile affects success of therapy, this suggests that different drugs might express different efficacy pending on duration of the pain in patients with PDN.

Efficient conditioned pain modulation despite pain persistence in painful diabetic neuropathy


Orginally Published At: PAIN Reports

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Effect of gastroretentive gabapentin (Gralise) on postmastectomy pain syndrome: a proof-of-principle open-label study

imageIntroduction:
Chronic pain is a common and debilitating complication following breast surgery. One of the most challenging for treatment is the neuropathic pain condition, postmastectomy pain syndrome (PMPS). Gabapentin is a pharmacotherapy for neuropathic pain disorders; however, its once-daily, gastroretentive formulation, Gralise, has not been evaluated in PMPS.
Objective:
To evaluate the safety and effectiveness of Gralise in patients with moderate-to-severe PMPS.
Methods:
The primary effectiveness endpoint was a change in the worst pain intensity score from baseline to completion of 8 weeks of Gralise therapy. The secondary endpoints included the change in mood, coping behavior, sleep, and function. Sensitivity to experimental stimuli was tested before and after treatment via quantitative sensory testing. The incidence and type of adverse event were used to evaluate the safety and tolerability of Gralise.
Results:
Twenty-one patients with confirmed moderate-to-severe PMPS were enrolled. Nineteen of 21 (90.5%) patients completed the 8-week treatment with Gralise. A significant positive change was found in pain intensity, pain impact, and sleep. There was no change in sensory testing scores. Of total, 63.16% of patients reported reduction in present pain, 78.95% in average pain, 89.47% in worst pain, and 84.21% in overall pain severity at posttreatment visit. No significant adverse effects were noted in the study.
Limitations:
Variation in type of breast surgery, small sample size, lack of placebo control.
Conclusion:
There was a significant improvement in pain and sleep, and Gralise was well tolerated in patients with PMPS. Further investigation is warranted.

Effect of gastroretentive gabapentin (Gralise) on postmastectomy pain syndrome: a proof-of-principle open-label study


Orginally Published At: PAIN Reports

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Spontaneous recurrent episodes of wrist pain in a 16-year-old girl: a case of complex regional pain syndrome

imageIntroduction: Complex regional pain syndromes (CRPS) are disabling pain syndromes that can develop after minor tissue injury or trauma and are characterized by sensory, motor, and autonomic abnormalities distributed in a glove-like or stocking-like manner. Complex regional pain syndrome is well known in adults, but is relatively rare in children. Most of the reported cases of CRPS in children are clinical diagnoses that are not supported by examinations such as three-phase bone scintigraphy. Furthermore, different centres often use different diagnostic criteria for CRPS, which sometimes questions the diagnosis of CRPS.
Objective/Methods: Although, recurrences and in particular relapses of CRPS have been observed, a periodically, nearly self-limiting course of disease without any residues in pain-free episodes and without any new obvious injury in CRPS is rather unusual. We present the case of a 16-year-old girl who reported recurrent spontaneous pain which lasted for 2 to 3 weeks and occurred approximately 2 times a year after the patient had experienced a mild trauma 3 years ago.
Results: The pain was accompanied by swelling, temperature asymmetry, and decreased range of motion of the right hand without any complains in pain-free episodes. Recurrent symptoms occurred without any obvious trauma. Diagnosis of CRPS was made from clinical findings including quantitative sensory testing, increased periarticular radioisotope uptake in the delayed phase of three-phase bone scintigraphy and examination during anaesthesia. Multimodal inpatient pain treatment resolved her symptoms substantially.
Conclusion: Complex regional pain syndrome in children may imitate rheumatologic diseases, and the course is different from adults despite similar clinical findings.

Spontaneous recurrent episodes of wrist pain in a 16-year-old girl: a case of complex regional pain syndrome


Orginally Published At: PAIN Reports