Level Of Allodynia Research Articles

Long-Term Prophylactic Transcranial Direct Current Stimulation Ameliorates Allodynia and Improves Clinical Outcomes in Individuals With Migraine

ObjectivesMigraine is a common and substantially debilitating disorder that may associate with allodynia, a marker of central sensitization in the pain circuits. Several unmet needs, like limited adherence to drugs due to adverse events and cost-effectivity, still occur in the prophylactic treatment of migraine. Transcranial direct current stimulation (tDCS) has recently been indicated to be beneficial in individuals with migraine with and without allodynia. However, to our knowledge, there are no studies evaluating the efficacy of six-month tDCS in migraine. Materials and MethodsThis study was a randomized double-blind parallel-group sham-controlled five-month extension study after a one-month lead-in trial of tDCS in individuals with migraine. A total of 23 individuals with migraine with allodynia who completed the lead-in trial were recruited after their consent and were administered three consecutive sessions of 2-mA anodal 20-minute tDCS over the left primary motor cortex every month for an additional five months. Pain-related outcomes were determined using monthly headache diaries. Allodynia, depression, anxiety, and disability because of migraine also were assessed throughout the study. ResultsImprovements in allodynia levels, attack frequency, number of rescue medications, and attack duration were higher, and mostly gradual during the trial, in the active group. Migraine Disability Scale grades also were lower in the active group, whereas no between-group differences were found in depression and anxiety scores. Higher responder rates of migraine attack frequency (56.8% vs 25%), number of headache days (56% vs 16.7%), and migraine attack duration (90.9% vs 8.3%) were observed after six-month tDCS in the active group than in the sham group. ConclusionsLong-term extended tDCS is shown to be a safe, efficacious, and plausible modality for prophylactic treatment in individuals with migraine with allodynia. SignificanceLong-term extended tDCS can alleviate allodynia, which is an indicator of drug resistance and chronicity, and meet the goals of prophylactic treatment in individuals with migraine with allodynia.

The role of low level laser therapy on neuropathic pain relief and interleukin-6 expression following spinal cord injury: An experimental study

IntroductionThe effect of Low Level Laser Therapy (LLLT) as a non-invasive treatment of spinal cord injury (SCI) is still under investigation. Therefore, the present study aimed to evaluate the effectiveness of LLLT on neuropathic pain and interleukin-6 (IL-6) expression following SCI in male rats. Methods46 adult male rats were divided into 5 groups of control, SCI, treatment with methylprednisolone sodium succinate (MPSS), 1-week LLLT and 2-week LLLT. Animals underwent behavioral evaluations for motor behavior, level of allodynia and hyperalgesia every week. At the end, spinal cord was extracted and IL-6 level was assessed by ELISA method. ResultsTreatment with MPSS and 2-week LLLT had led to motor function recovery (df: 24, 145; F=223.5; p <0.001). SCI did not affect mechanical (df: 24, 145; F=0.5; p=0.09), and cold allodynia (df: 24, 145; F=0.3; p=0.17) but significantly increased mechanical (df: 24, 145; F=21.4; p<0.001) and heat hyperalgesia (df: 24, 145; F=16.1; p<0.001). Treatment with MPSS and 1 and 2-weeks LLLT improved mechanical hyperalgesia (p<0.05) and heat hyperalgesia (p<0.01). The increased level of IL-6 following SCI was also compensated by administration of MPSS or LLLT (df: 4, 10; F=8.74; p=0.003). ConclusionFindings show that long periods of LLLT have better effects in improving the complication of SCI. In summation, since LLLT does not cause the side effects of MPSS, long-term use of LLLT may be a proper alternative for MPSS in decreasing post SCI side effects.

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Effect of spinal cord stimulation in an animal model of neuropathic pain relates to degree of tactile “allodynia”

Spinal cord stimulation (SCS) is an established treatment for chronic neuropathic pain. However, in recent studies conflicting results regarding the effect of SCS were noted in a selected group of patients suffering from complex regional pain syndrome and mechanical allodynia. In the present study we investigated the pain relieving effect of SCS in a rat experimental model of neuropathic pain as related to the severity of mechanical allodynia. Adult male rats (n=45) were submitted to a unilateral sciatic nerve ligation. The level of allodynia was tested using the withdrawal response to tactile stimuli with the von Frey test. A portion of these rats developed marked tactile hypersensitivity in the nerve-lesioned paw (von Frey test), similar to “tactile allodynia” observed after nerve injury in humans. Prior to SCS treatment the rats were subdivided into three groups based on the level of allodynia: mild, moderate and severe. All allodynic rats were treated with SCS (n=27) for 30 min (f=50 Hz; pulse width 0.2 ms and stimulation at 2/3 of motor threshold) at 16 days post-injury. Our data demonstrate a differential effect of SCS related to the severity of the mechanical allodynia. SCS leads to a faster and better pain relief in mildly allodynic rats as compared with the more severely allodynic rats. Thus, we suggest that the selection and subdivision of patient groups similar to those defined in our experimental setting (mild, moderate and severe allodynic) may provide better pre-treatment prediction of possible therapeutic benefits of SCS.

The correlation between dietary soy phytoestrogens and neuropathic pain behavior in rats after partial denervation.

Soy diets suppress the development of neuropathic pain behavior in rats undergoing partial sciatic nerve ligation (PSL) injury. Phytoestrogens, plant isoflavones and lignans, abundantly found in soy products, have powerful estrogenic properties. Because, in some preparations, steroid estrogens were found to exert antinociception, we examined whether the analgesic effect of dietary soy is mediated by phytoestrogens. Male Wistar rats were fed five different diets containing 8-180 microg of phytoestrogens per gram. These diets were administered 2 wk before and 2 wk after PSL injury. Levels of tactile allodynia and mechanical and heat hyperalgesia of these rats were determined on Days 3, 8, and 14 after PSL injury. Plasma levels of two major phytoestrogens (genistein and daidzein) and two daidzein metabolites (equol and dihydrodaidzein) were assessed on Day 14 postoperatively. We found that the plasma concentration of these phytoestrogens and the levels of allodynia and hyperalgesia varied highly among dietary groups. Average plasma concentrations of phytoestrogens were associated with reduced levels of tactile allodynia and mechanical hyperalgesia, but not with reduced heat allodynia. Low and high plasma phytoestrogen levels were not analgesic in these tests. This report is the first to show that, at certain plasma concentrations, phytoestrogens reduce neuropathic pain in rats. Dietary soy suppresses neuropathic pain in rats after partial sciatic nerve ligation. Some of the pain-suppression properties of soy can be attributed to phytoestrogens, isoflavones abundantly found in soy products. Average, but not low or high, plasma levels of phytoestrogens are associated with analgesia.

The Correlation Between Dietary Soy Phytoestrogens and Neuropathic Pain Behavior in Rats After Partial Denervation

Soy diets suppress the development of neuropathic pain behavior in rats undergoing partial sciatic nerve ligation (PSL) injury. Phytoestrogens, plant isoflavones and lignans, abundantly found in soy products, have powerful estrogenic properties. Because, in some preparations, steroid estrogens were found to exert antinociception, we examined whether the analgesic effect of dietary soy is mediated by phytoestrogens. Male Wistar rats were fed five different diets containing 8–180 μg of phytoestrogens per gram. These diets were administered 2 wk before and 2 wk after PSL injury. Levels of tactile allodynia and mechanical and heat hyperalgesia of these rats were determined on Days 3, 8, and 14 after PSL injury. Plasma levels of two major phytoestrogens (genistein and daidzein) and two daidzein metabolites (equol and dihydrodaidzein) were assessed on Day 14 postoperatively. We found that the plasma concentration of these phytoestrogens and the levels of allodynia and hyperalgesia varied highly among dietary groups. Average plasma concentrations of phytoestrogens were associated with reduced levels of tactile allodynia and mechanical hyperalgesia, but not with reduced heat allodynia. Low and high plasma phytoestrogen levels were not analgesic in these tests. This report is the first to show that, at certain plasma concentrations, phytoestrogens reduce neuropathic pain in rats.

Soy-containing diet suppresses chronic neuropathic sensory disorders in rats.

Partial sciatic nerve ligation (PSL) in rodents produces chronic neuropathic sensory disorders resembling neuropathic pain in humans. We previously reported that levels of allodynia and hyperalgesia after PSL injury were markedly attenuated by consumption of soy-containing diets. Here we aimed to show that dietary effect on pain behavior is not specific to a certain laboratory. For this purpose, experiments were conducted in a different laboratory (Baltimore rather than Jerusalem) and a different rat strain (Wistar rather than Sabra), with additional and different testing methods (radiant heat from a lamp rather than a CO(2) laser). Rats were fed two soy-free diets and a soy-containing one for 28 days. The sensitivity of rats to nonnoxious and noxious stimuli was determined before PSL injury, and levels of neuropathic sensory disorders were determined after it. We found that consuming the soy-containing diet prevented development of tactile and heat allodynia, but not mechanical hyperalgesia. This dietary effect was not correlated with calorie intake and weight gain or dietary concentration of fat and carbohydrates. We conclude that, regardless of experimental site, diet markedly affects chronic neuropathic sensory disorders in rats and should be standardized in animal models of pain. Levels of chronic sensory disorders in a rat model of allodynia and hyperalgesia after partial sciatic nerve ligation depend on the consumption of a soy-containing diet. Further studies are needed to determine the role of diet in humans with chronic pain.

Correlation of intact sensibility and neuropathic pain-related behaviors in eight inbred and outbred rat strains and selection lines

In some rat strains, total hindpaw denervation triggers autotomy, a behavior of self mutilation presumably related to neuropathic pain. Partial sciatic ligation (PSL) in rats produces tactile allodynia and heat hyperalgesia but not autotomy. Our aims in this study were to examine: (1) whether sensibility of intact rats to noxious and non-noxious stimuli is strain-dependent; (2) whether sensibility of intact rats could predict levels of autotomy, or of allodynia and hyperalgesia in the PSL model; and (3) whether autotomy levels are correlated with levels of allodynia or hyperalgesia. Here we report that in two inbred rat strains (Lewis and Fisher 344), two outbred rat strains (Sabra and Sprague–Dawley) and four selection lines of rats (Genetically Epilepsy-Prone Rats, High Autotomy, Low Autotomy and Flinders Sensitive Line), tactile sensitivity and response duration to noxious heat of intact animals were strain-dependent. Levels of autotomy following hindpaw denervation and of allodynia and hyperalgesia in the PSL model were also strain-dependent. Thus, these traits are determined in part by genetic factors. Sensory sensibility of intact rats was not correlated with levels of autotomy following total denervation, or allodynia and hyperalgesia following partial denervation. We suggest that preoperative sensibility of intact rats is not a predictor of levels of neuropathic disorders following nerve injury. Likewise, no correlation was found between autotomy, allodynia and hyperalgesia, suggesting that neuropathic pain behaviors triggered by nerve injury of different etiologies are mediated by differing mechanisms.