Abstract

Neuropathic pain is an intractable chronic pain condition that is mainly caused by allodynia. We had previously reported that intra-plantar administration of bergamot essential oil (BEO) containing an aromatic compound significantly suppressed partial sciatic nerve ligation (PSNL)-induced mechanical allodynia via opioid mu receptors in mice. However, it has also been reported that the inhalation of BEO reduced formalin-induced nociceptive responses. Therefore, we aimed to elucidate whether the analgesic action of BEO is mediated by olfactory stimulation through volatile components. In the current study, BEO was continuously administered with an osmotic pump during PSNL surgery, and the effects on mice behavior were examined pharmacologically using a double activity monitoring system, which can detect two-dimensional planar motion in a cage with an infrared beam sensor as well as active motion with a running wheel. Here, we report that the two-dimensional planar activity significantly increased in mice with PSNL in the light phase (from 8 o’clock to 20 o’clock) but not in the dark phase (from 20 o’clock to 8 o’clock) from the second day after surgery. However, this increase was not observed when BEO was continuously administered. The effect of BEO on the two-dimensional planar counts in mice with PSNL was antagonized by naloxone hydrochloride. Regarding the running wheel activity, the number of rotations decreased by PSNL in the dark phase from the 8th day after surgery. However, this was not apparent with BEO use. The effect of BEO on the number of rotations was also antagonized by naloxone hydrochloride. Furthermore, inhalation of BEO in PSNL mice did not affect mechanical allodynia or the two-dimensional planar motion or running wheel activities. These findings indicate that BEO exhibits an analgesic action, which is mediated by opioid receptors and not by the olfactory system.

Highlights

  • Neuropathic pain is a chronic condition that occurs after nerve compression due to cancer, diabetes, herpes virus infection, and autoimmune diseases (Woolf and Mannion, 1999)

  • We investigated the behavioral phenotype of partial sciatic nerve ligation (PSNL) mice on the running wheel activity

  • The effect of bergamot essential oil (BEO) was significantly antagonized 2 days after co-administration with naloxone hydrochloride (12 days after surgery; PSNL-jojoba wax: 972.00 ± 543.95, PSNL-BEO: 4,070.33 ± 693.64, PSNL-BEO/ Naloxone: 1,431.33 ± 287.24) (Figure 4E). These results indicate that the continuous administration of BEO suppressed the decrease in the running wheel activity that was observed in PSNL mice via opioid receptors

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Summary

Introduction

Neuropathic pain is a chronic condition that occurs after nerve compression due to cancer, diabetes, herpes virus infection, and autoimmune diseases (Woolf and Mannion, 1999). Millions of patients worldwide endure neuropathic pain (Tsuda et al, 2005). One troubling and characteristic symptom of neuropathic pain is hypersensitivity to usually harmless stimuli, a condition known as “tactile allodynia,” which is often resistant to NSAIDs and opioids (Backonja and Glanzman, 2003). Various models have been devised to reproduce disease-like conditions in rodents, such as diabetic neuropathy, chemotherapy-induced neuropathic pain, antiretroviral druginduced neuropathy, and spinal and peripheral nerve damage. It has become clear that chronic pain can affect cognitive behavior in animal models just as it does in humans (Guida et al, 2020). The establishment of treatments for neuropathic pain is an important issue in terms of reducing anxiety and depression

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