The present study examined the antinociceptive effect of the ethanolic extract from Melissa officinalis L. and of the rosmarinic acid in chemical behavioral models of nociception and investigates some of the mechanisms underlying this effect. The extract (3-1000 mg/kg), given orally (p.o.) 1 h prior to testing, produced dose-dependent inhibition of acetic acid-induced visceral pain, with ID50 value of 241.9 mg/kg. In the formalin test, the extract (30-1000 mg/kg, p.o.) also caused significant inhibition of both, the early (neurogenic pain) and the late (inflammatory pain), phases of formalin-induced licking. The extract (10-1000 mg/kg, p.o.) also caused significant and dose-dependent inhibition of glutamate-induced pain, with ID50 value of 198.5 mg/kg. Furthermore, the rosmarinic acid (0.3-3 mg/kg), given p.o. 1 h prior, produced dose-related inhibition of glutamate-induced pain, with ID50 value of 2.64 mg/kg. The antinociception caused by the extract (100 mg/kg, p.o.) in the glutamate test was significantly attenuated by intraperitoneal (i.p.) treatment of mice with atropine (1 mg/kg), mecamylamine (2 mg/kg) or l-arginine (40 mg/kg). In contrast, the extract (100 mg/kg, p.o.) antinociception was not affected by i.p. treatment with naloxone (1 mg/kg) or D-arginine (40 mg/kg). It was also not associated with non-specific effects, such as muscle relaxation or sedation. Collectively, the present results suggest that the extract produced dose-related antinociception in several models of chemical pain through mechanisms that involved cholinergic systems (i.e. through muscarinic and nicotinic acetylcholine receptors) and the L-arginine-nitric oxide pathway. In addition, the rosmarinic acid contained in this plant appears to contribute for the antinociceptive property of the extract. Moreover, the antinociceptive action demonstrated in the present study supports, at least partly, the ethnomedical uses of this plant.

In this study, we determined the anti-inflammatory effect of manual acupuncture at the Sanyinjiao or Spleen 6 (SP6) point on carrageenan-induced peritonitis in mice and investigated mechanisms that may underlie this effect. In the first set of experiments, male Swiss mice were allocated into five groups: the control (sterile saline), dexamethasone (DEXA), invasive sham-acupuncture (non-acupoint), SP6 acupuncture and carrageenan-treated groups. Ten minutes after needle retention or 30 min after DEXA treatment, mice received an intraperitoneal injection of carrageenan (750 μg/mouse). After 4 h, total leukocyte and differential cell counts (neutrophils and mononuclear), myeloperoxidase (MPO) activity, vascular permeability and cytokine levels were evaluated. In another set of experiments, adrenalectomized (ADX) mice were used to study the involvement of the adrenal gland on the therapeutic effects of acupuncture. Mice were allocated into two groups: the ADX and sham-operated animals (Sham ADX) that were subdivided into four subgroups each: the control (sterile saline), DEXA, SP6 acupuncture and carrageenan-treated groups. The SP6 and DEXA treatments inhibited the inflammatory cell infiltration, vascular permeability and MPO activity in carrageenan-injected mice. In addition, the SP6 treatment also increased interleukin (IL)-10 levels. In contrast, when the animals were adrenalectomized, the SP6 treatment failed to reduce total leukocyte and the plasma extravasation. In conclusion, this study clearly demonstrates the anti-inflammatory effect of SP6 acupuncture in a model of carrageenan-induced peritonitis. Our results demonstrated that SP6 acupuncture depends of the adrenal glands and increased IL-10 levels to produce its anti-inflammatory action.

No abstract

Lesions of peripheral nerves lead to pain, hyperalgesia, and psychological comorbidities. However, the relationship between mood disorders and neuropathic pain is unclear, as well as the underlying mechanisms related to these disorders. Therefore, we investigated if nerve injury induces depression, anxiety, and cognitive impairment and if there were changes in cytokines, growth factors, and glial cell activation in cortical sites involved in processing pain and mood in animals with nerve injury. Nerve injury was induced by partial sciatic nerve ligation (PSNL) in male Swiss mice and compared to sham-operated animals. Nociceptive behavioral tests to mechanical and thermal (heat and cold) stimuli confirmed the development of hyperalgesia. We further examined mood disorders and memory behaviors. We show nerve injury induces a decrease in mechanical withdrawal thresholds and thermal latency to heat and cold. We also show that nerve injury causes depressive-like and anxiety-like behaviors as well as impairment in short-term memory in mice. There were increases in proinflammatory cytokines as well as Brain-Derived Neurotrophic Factor (BDNF) in the injured nerve. In the spinal cord, there were increases in both pro and anti-inflammatory cytokines, as well as of BDNF and Nerve Growth Factor (NGF). Further, in our data was a decrease in the density of microglia and astrocytes in the hippocampus and increased microglial density in the prefrontal cortex, areas associated with neuropathic pain conditions.

No abstract

While patients with carpal tunnel syndrome (CTS) report pain and paresthesia in conjunction with decreased median nerve conduction velocities, patients with idiopathic hand pain (IHP) report similar symptoms but with normal nerve conduction. While brain plasticity has been reported for CTS, the effects of acupuncture on structural plasticity in either IHP or CTS are unknown. We evaluated 19 IHP patients, 21 CTS patients, and 13 healthy controls (HC) with structural T1weighted MRI at 3T (Siemens Trio) before and after 8weeks of acupuncture. Symptoms were evaluated with the Boston Carpal Tunnel Syndrome Questionnaire (BCTSQ) before, after, and 3-months following acupuncture therapy. Acupuncture included 2Hz electrical stimulation at acupoints PC7 and TW5 near the affected wrist. Gray matter thickness data were contrast between IHP and CTS at baseline, and before versus after acupuncture. Difference maps were calculated, cluster corrected for multiple comparisons at p=0.05. Cortical thickness data were also correlated with BCTSQ change. BCTSQ symptoms decreased following acupuncture, retained at 3-month follow-up in both groups (IP; baseline: 2.760.6, mean6SD, post-acup: 1.960.5, 3-months: 1.760.5, CTS; baseline: 2.860.6, post-acup: 2.160.7, 3-months: 2.260.7, p<0.01). At baseline, cortical thickness in bilateral insulae was significantly greater in IHP compared to CTS (p<0.05), and both groups showed, on average, reduced thickness compared to HC. Following acupuncture in IHP, cortical thickness was significantly increased in bilateral insulae. Furthermore, insula thickness increase was negatively correlated with post-acupuncture symptom change (r=-0.53, p=0.05). Thus, greater thickness increase was associated with greater reduction in symptom severity. These changes were not seen for CTS. Symptoms were reduced by acupuncture and sustained during 3-months follow up. Increased insula thickness postacupuncture was correlated with symptom reduction for IHP. Thus, cortical thickness may be sensitive to improvements in symptomatology, but not when such symptoms are maintained by a peripheral lesion. Funded by NCCAM, NIH.NADA acupuncture protocol is the most common form of acupuncture treatment for substance addiction in the US and Europe. This protocol has been utilized as an adjunctive therapy for addiction treatment, behavioral health, cancer and blood disorders. The protocol uses five ear points: shenmen, sympathetic, kidney, liver, and lung. Clinical studies had shown contradicting results regarding the efficacy of NADA protocol in controlling opioid-induced withdrawal and other craving-related symptoms. The mechanism by which it serves as a successful treatment remains inconclusive, therefore establishing an animal model of NADA acupuncture treatment is important. Repeated morphine administration in rodents has been shown to produce locomotor sensitization. In addition, discontinuation of morphine treatment results in withdrawal symptoms, including increased pain sensitivity. We administered rats with 10 mg/kg of mo...