All-trans retinoic acid-induced focal myositis, synovitis, and mononeuritis.

All-trans retinoic acid has revolutionized the treatment of acute promyelocytic leukemia, but this therapy is often complicated by the all-trans retinoic acid syndrome. Here we report a patient with newly diagnosed acute promyelocytic leukemia who developed acute focal myositis, synovitis, and possible vasculitis, after receiving all-trans retinoic acid therapy. We review the existing literature on this rare clinical entity, all-trans retinoic acid-induced myositis. This condition can manifest as fever, myalgia, arthralgia, and Sweet syndrome, accompanied by distinct magnetic resonance findings involving the lower extremity musculature. Treatment consists of discontinuation of the offending drug and often high dose corticosteroids.

Activity of new NOP receptor ligands in a rat peripheral mononeuropathy model: potentiation of morphine anti-allodynic activity by NOP receptor antagonists.

The effect of new NOP receptor agonists and antagonists in the rat chronic constriction injury model was investigated. Intraperitoneally administered NOP receptor agonist SR14150 and antagonists SR16430 and SR14148, had no effect on mechanical allodynia when given alone. The nonselective NOP/mu-opioid receptor agonist SR16435, however, produced an anti-allodynic response, similar to morphine and reversible by naloxone. Notably, co-administration of the NOP receptor antagonists potentiated the anti-allodynic activity of both morphine and SR16435. Increased levels of the NOP receptor are implicated in the reduced efficacy of morphine in neuropathic pain. Our results suggest the utility of NOP receptor antagonists for potentiating opioid efficacy in chronic pain.

Omalgia pruriginosa / Pruriginous omodynia

La notalgia parestésica es una mononeuropatía sensitiva producida por atrapamiento de los ramos dorsales de las raíces espinales de D2 a D6, debido a que estos nervios se angulan 90° al pasar por la musculatura paraespinal. Se desconoce su causa, pero se ha visto relacionada con alteraciones en la estática de la columna a ese nivel (artrosis, escoliosis). Parestesias, prurito y quemazón son los síntomas más frecuentes y, junto con el hallazgo de una placa hiperpigmentada en dicha localización, constituyen los pilares de su diagnóstico. La electroneurografía muestra signos de denervación en las raíces afectadas. Únicamente la capsaicina tópica ha demostrado eficacia en ensayos clínicos. Otras terapias descritas en la literatura son la acupuntura, el bloqueo anestésico paravertebral local, la fisioterapia y la oxcarbazepina (AU)

Notalgia paresthetica is a sensory mononeuropathy producedby the dorsal spinal nerve root branch entrapmentfrom D2 to D6 because these nerves are angles 90° when passingthrough the paraspinal musculature. Its cause is unknownbut it has been observed to be related with alterationsin the spinal cord statics at this level (arthritis, scoliosis). Paresthesias,pruritus and burning sensation are the most frequentsymptoms. Together with the finding of a hyperpigmentedplaque at that location, they are the mainstay of itsdiagnosis. The electroneurography shows signs of denervationin the affected roots. Only topical capsaicin has beenshown to be effective in clinical trials. Other therapies describedin the literature are acupunture, local paravertebralblock anesthesia, physical therapy and oxcarbazepine (AU)

A synthetic kainoid, (2S,3R,4R)-3-carboxymethyl-4-(phenylthio)pyrrolidine-2-carboxylic acid (PSPA-1) serves as a novel anti-allodynic agent for neuropathic pain.

In spite of prominent progress in basic pain research, neuropathic pain remains a significant medical problem, because it is often poorly relieved by conventional analgesics. Thus this situation encourages us to make more sophisticated efforts toward the discovery of new analgesics. We previously showed that i.t. administration of acromelic acid-A (ACRO-A), a Japanese mushroom poison, provoked prominent tactile pain (allodynia) at an extremely low dose of 1 fg/mouse. In the present study we synthesized ACRO-A analogues (2S,3R,4R)-3-carboxymethyl-4-phenoxypyrrolidine-2-carboxylic acid (POPA-2) and (2S,3R,4R)-3-carboxymethyl-4-(phenylthio)pyrrolidine-2-carboxylic acid (PSPA-1) chemically and examined their ability to induce allodynia in conscious mice. Whereas POPA-2 induced allodynia at extremely low doses from 1 to 100 fg/mouse, similar to ACRO-A, PSPA-1 did not induce allodynia; rather, it inhibited the ACRO-A-induced allodynia with an ID(50) value (95% confidence limits) of 2.19 fg/mouse (0.04-31.8 fg/mouse). Furthermore, PSPA-1 relieved neuropathic pain produced by L5 spinal nerve transection on day 7 after the operation in a dose-dependent manner from 1 to 100 pg/mouse. In contrast, it did not affect thermal or mechanical nociception or inflammatory pain. PSPA-1 reduced the increase in neuronal nitric oxide synthase activity in the spinal cord of neuropathic pain mice assessed by NADPH-diaphorase histochemistry and blocked the allodynia induced by N-methyl-d-aspartate. These results demonstrate that PSPA-1 may represent a novel class of anti-allodynic agents for neuropathic pain acting by blocking the glutamate-nitric oxide pathway.

Antinociceptive activity of the selective iNOS inhibitor AR-C102222 in rodent models of inflammatory, neuropathic and post-operative pain.

Nitric oxide generated by the nitric oxide synthase (NOS) isoforms contributes to pain processing. The selective inhibition of iNOS might represent a novel, therapeutic target for the development of antinociceptive compounds. However, few isoform-selective inhibitors of NOS have been developed. The present experiments examined the anti-inflammatory and antinociceptive activity of a selective inducible nitric oxide (iNOS) inhibitor, AR-C102222, on arachidonic acid-induced ear inflammation, Freund's complete adjuvant (FCA)-induced hyperalgesia, acetic acid-induced writhing, and tactile allodynia produced by L5 spinal nerve ligation (L5 SNL) or hindpaw incision (INC). AR-C102222 at a dose of 100mg/kg p.o., significantly reduced inflammation produced by the application of arachidonic acid to the ear, attenuated FCA-induced mechanical hyperalgesia, and attenuated acetic acid-induced writhing. In the L5 SNL and INC surgical procedures, tactile allodynia produced by both procedures was significantly reduced by 30mg/kg i.p. of AR-C102222. These data demonstrate that the selective inhibition of iNOS produces antinociception in different models of pain and suggest that the iNOS-NO system plays a role in pain processing.