Many of analgesics and analgesic adjuvants act on nerve conduction and synaptic transmission in the nervous system to inhibit nociceptive transmission. It has not been fully examined how nerve conduction inhibition leading to antinociception differs in extent among various analgesics and analgesic adjuvants. We examined quantitatively their actions on fast–conducting compound action potentials (CAPs) recorded from the frog sciatic nerve. Drugs tested were local anesthetics, opioids, adrenoceptor agonists, antiepileptics, antidepressants and non–steroidal anti–inflam­matory drugs (NSAIDs). As a result, we found that many of their drugs reduce the peak amplitude of the CAPs in a manner dependent on their chemical structures. Consistent with voltage–gated Na⁺–channel inhibition produced by local anesthetics, CAP peak amplitudes were reduced by procaine, cocaine, tetracaine, prilocaine, lidocaine, ropivacaine, levobupivacaine and pramoxine with the half–maximal inhibitory concentration (IC50) values of 2.2, 0.80, 0.013, 1.8, 0.74, 0.34, 0.23 and 0.21 mM, respectively. A weak opioid tramadol reduced CAP peak amplitude­s (IC₅₀ = 2.3 mM) more effectively than its metabolite mono–O–demethyl–tramadol; this distinction was attributed to such a difference in chemical structure that tramadol and mono–O–demethyl–tramadol have –OCH₃ and –OH bound to a benzene ring, respectively. Moreover, a sequence of CAP peak amplitude reductions produced by various opioids was ethylmorphine (IC₅₀ = 4.6 mM) > codeine > morphine, i.e., this reduction enhanced in extent with an increase in the number of –CH₂. α₂–Adrenoceptor agonist dexmedetomidine reduced CAP peak amplitudes with an IC₅₀ value of 0.40 mM. Other α₂ adrenoceptor agonists, oxymethazoline (IC₅₀ = 1.5 mM) and clonidine, also inhibited CAPs with potencies less than dexmedetomidine while adrenaline, noradrenaline, an α₁ adrenoceptor agonist phenylephrine and a β–adrenoceptor agonist isoproterenol had no effect on CAPs. Antiepileptics, lamotrigine and carbamazepine, reduced CAP peak amplitudes with the IC₅₀ values of 0.44 and 0.50 mM, respectively. CAP peak amplitudes were reduced by a small extent by oxcarbazepine and phenytoin. On the other hand, gabapentin, topiramate and sodium valproate had no effect on CAPs. With respect to antidepressants, amitriptyline, duloxetine, maprotiline, fluoxetine, desipramine and trazodone reduced CAP peak amplitudes with the IC₅₀ values of 0.26, 0.23, 0.95, 1.5, 1.6 and ca. 1.0 mM, respectively. Acetic acid–based NSAIDs (diclofenac and aceclofenac) reduced CAP peak amplitudes with the IC₅₀ values of 0.94 and 0.47 mM, respectively. Other acetic acid–based NSAIDs (indomethacin, etodolac and acemetacin) also inhibited CAPs; sulindac and felbinac had no effect on CAP amplitudes. A similar CAP inhibition was produced by fenamic acid–based NSAIDs [tolfenamic acid, meclofenamic acid and flufenamic acid (IC₅₀ values: 0.29, 0.19 and 0.22 mM, respectively)]. On the other hand, salicylic acid–based (aspirin), propionic acid–based (ketoprofen, ibuprofen, naproxen, loxoprofen and flurbiprofen) and enolic acid–based (meloxicam and piroxicam) NSAIDs had no effect on CAPs. In conclusion, CAP inhibitions produced by local anesthetics were partly comparable in extent to those of α₂ adrenoceptor agonists, antiepileptics, antidepressants and NSAIDs; opioids inhibited CAPs less potently than their drugs. It is suggested that analgesics and analgesic adjuvants inhibit nerve conduction in a manner dependent on their chemical structures.

The aim of this study was to compare pain sensitivity between the follicular and luteal phases of the menstrual cycle in Japanese young adults. Fifteen females participat­ed in this randomized control trial with crossover design. The pain threshold (defined as the temperature when the subject started to feel pain) was measured using a heat pain stimulator on the short flexor muscle of the thumb. For each subject, the stimulus was performed 10 times, alternating between the right and left hand. Pain reactivity was evaluated using a self–identified threshold of heat pain, salivary alpha amylase, emotional evaluation using a profile of mood states and visual analog scale scores. After comparative analysis, we found that pain threshold under the follicular phase was significantly increased compared to that under the luteal phase, indicating that the menstrual cycle would influence the severity of pain perception. Pain sensitivity under the luteal phase is more sensitive to nociceptive stimuli than those under the follicular phase. We therefore need to conduct pain management with paying heed to the menstrual cycle. Additionally, young women in reproductive–age should be more protective in pain management during the luteal phase of their menstrual cycle.

Chronic pain is known to get worse under the influence of weather change (tempera­ture, humidity, pressure). This is generally called “weather–related pain”. The author believes that the pressure sensor in the inner ear and the autonomic nervous system imbalance are involved in the mechanism of worsening pain and associated symptoms due to a decrease in atmospheric pressure. In addition, the activation mechanism of the cold receptor on skin occurs in chronic pain, which is considered to be the main role of the mechanism of aggravation of chronic pain under low tem­perature environments.

It is said that chronic pain turns worse when weather worsens than before. However, there are few articles showing weather and the relations of the pain. Our clinic is a medical institution of the pain clinic single department, and most of the patients having a medical examination are accompanied by chronic pain. In addition, we have the list Visual Analogue Scale (VAS) in all consultation patients foreign than 2013 at consultation. After checking association about the weather with VAS at consultation, in temperature, the humidity, the atmospheric pressure, it was thought that a change of the atmospheric pressure was related to the strength of the pain. By the disease distinction, we recognized meaningful correlation in herpes zoster referred pain, osteoarthritis of the knee, osteoarthritis of the hip in VAS at most atmospheric pressure drop quantity and consultation by the division at specific time.

Although migraine has been reported to have different inducing factors, changes in weather parameters such as atmospheric pressure, rain, humidity, temperature, wind, and lightning are well known important environmental factors. In recent years, reports of abnormal weather conditions such as heat waves in summer, heavy snow in winter, localized heavy rain, and abnormally light rain, as well as tropical cyclones are increasing. In today’s extreme weather conditions, the worsening, diver­sification, and chronicity of migraine symptoms is concerning, and a higher level of treatment for migraine is required than ever before. Drug therapy is used as the principal treatment for migraine. If the acute treatment alone interferes with daily life, the principle is to combine daily preventive therapies to reduce the frequency, severity, and duration of the migraine attacks. However, there are several cases wherein migraine is poorly controlled only with their combination. Several patients with migraine experience prodromal symptoms, including stiff neck and shoulder as well as sensitivity to light and sound, before migraine attacks. In recent years, it has been reported that sensors for detecting atmospheric pressure exist in the vestibular part of the inner ear, and it has been shown that changes in atmospheric pressure may activate the vestibular nerve activity. We reported that difenidol, a vestibular nerve modulator, was administered to prevent or alleviate migraine attacks during the prodromal phase caused by change in weather. Prevention during the prodromal phase and prevention based on weather prediction are new treatment strategies for migraine. In today’s extreme weather conditions, 3–P therapy that combines the three treatment strategies of prevention, prodrome, and prediction is useful.

Patients who complain of chronic pain have various symptoms and complicated pathologies, and there are often cases in which the symptoms worsen due to weather changes. However, few studies have examined the nature of pain affected by weather changes. In this time, we investigated the characteristics of patients with weather–related pain. As results, their pain intensity is moderate and they can maintain moderate daily activity. But in psychosocial factors, they have low self–efficacy and high catastrophic thinking. As treatment for chronic pain, exercise therapy managed by a therapist is highly recommended in non–drug therapy. Patients with weather–related pain often complain at head and neck shoulders. Evidences on the effects of exercise therapy for these body parts have also been reported. We hope that capturing the characteristics of patients with weather–related pain will lead to more appropriate treatments tailored to the pathological condition of the patients.