Effect of palmitoylethanolamide on inflammatory and neuropathic pain in rats

다국어 초록 (Multilingual Abstract)

Background: A growing body of evidence suggests that neuroinflammation, which is characterized by infiltration of immune cells, activation of mast cells and glial cells, and production of inflammatory mediators in the peripheral and central nervous systems, plays an important role in the induction and maintenance of chronic pain. Palmitoylethanolamide (PEA), which is a type of N-acylethanolamide and a lipid, has an anti-inflammatory effect. Relative to the anti-inflammatory effect, little is known about its analgesic effect in chronic pain. This study aimed to determine whether PEA relieves chronic inflammatory and neuropathic pain.
Methods: Male Sprague-Dawley rats were injured by transection of the left L5 and L6 spinal nerves to induce neuropathic pain or were injected with monoiodoacetic acid into the synovial cavity of knee joints to induce inflammatory pain.
To assess the degree of pain, two kinds of stimuli - pressing von Frey filaments and wetting with acetone - were applied to the plantar surface of the rat to measure mechanical and cold sensitivity, respectively. Pain was measured by assessing behavioral responses, including paw withdrawal response threshold and paw withdrawal frequency upon stimulation.
Results: Neuropathic pain caused by spinal nerve transection (SNT) decreased the mechanical threshold and increased the frequency of response to acetone application. But, cold allodynia caused by SNT did not decrease the withdrawal frequency.
Mechanical hyperalgesia caused by chronic inflammation was significantly reduced by both intraperitoneal and intra-articular injections of PEA.
Conclusions: These outcomes revealed that PEA might be effective in relieving inflammatory and neuropathic pain, especially pain induced by mechanical hyperalgesia, but not cold allodynia.

참고문헌 (Reference)

1 Ochoa JL, "The triple cold syndrome. Cold hyperalgesia, cold hypoaesthesia and cold skin in peripheral nerve disease" 117 : 185-197, 1994

2 Wallace VC, "The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L-29) on pain behaviour in rodent models of neuropathy" 151 : 1117-1128, 2007

3 Jaggar SI, "The anti-hyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain" 76 : 189-199, 1998

4 Sheerin AH, "Selective antiepileptic effects of N-palmitoylethanolamide, a putative endocannabinoid" 45 : 1184-1188, 2004

5 Bacci C, "Randomized split-mouth study on postoperative effects of palmitoylethanolamide for impacted lower third molar surgery" 2011 : 917350-, 2011

6 Chaplan SR, "Quantitative assessment of tactile allodynia in the rat paw" 53 : 55-63, 1994

7 Mazzari S, "N-(2-hydroxyethyl)hexadecanamide is orally active in reducing edema formation and inflammatory hyperalgesia by down-modulating mast cell activation" 300 : 227-236, 1996

8 Kopsky DJ, "Multimodal stepped care approach with acupuncture and PPAR-α agonist palmitoylethanolamide in the treatment of a patient with multiple sclerosis and central neuropathic pain" 30 : 53-55, 2012

9 Calabrò RS, "Misdiagnosed chronic pelvic pain: pudendal neuralgia responding to a novel use of palmitoylethanolamide" 11 : 781-784, 2010

10 Facci L, "Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide" 92 : 3376-3380, 1995

11 Lee SE, "Involvement of substance P and calcitonin gene-related peptide in development and maintenance of neuropathic pain from spinal nerve injury model of rat" 58 : 245-249, 2007

12 Helyes Z, "Inhibitory effect of anandamide on resiniferatoxin-induced sensory neuropeptide release in vivo and neuropathic hyperalgesia in the rat" 73 : 2345-2353, 2003

13 Ross RA, "Inhibition of nitric oxide production in RAW264.7 macrophages by cannabinoids and palmitoylethanolamide" 401 : 121-130, 2000

14 Cobellis L, "Effectiveness of the association micronized N-Palmitoylethanolamine (PEA)-transpolydatin in the treatment of chronic pelvic pain related to endometriosis after laparoscopic assessment: a pilot study" 158 : 82-86, 2011

15 De Petrocellis L, "Effect on cancer cell proliferation of palmitoylethanolamide, a fatty acid amide interacting with both the cannabinoid and vanilloid signalling systems" 16 : 297-302, 2002

16 Calignano A, "Control of pain initiation by endogenous cannabinoids" 394 : 277-281, 1998

17 Smith FL, "Characterization of delta9-tetrahydrocannabinol and anandamide antinociception in nonarthritic and arthritic rats" 60 : 183-191, 1998

18 Petrosino S, "Changes in spinal and supraspinal endocannabinoid levels in neuropathic rats" 52 : 415-422, 2007

19 Berdyshev EV, "Cannabinoid receptors and the regulation of immune response" 108 : 169-190, 2000

20 Di Marzo V, "Cannabimimetic fatty acid derivatives in cancer and inflammation" 61 : 43-61, 2000

21 Calignano A, "Antinociceptive activity of the endogenous fatty acid amide, palmitylethanolamide" 419 : 191-198, 2001

22 Conti S, "Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid nabilone in a model of acute inflammation in the rat" 135 : 181-187, 2002

23 Richardson JD, "Antihyperalgesic effects of spinal cannabinoids" 345 : 145-153, 1998

24 Kim SH, "An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat" 50 : 355-363, 1992

25 Rodríguez de Fonseca F, "An anorexic lipid mediator regulated by feeding" 414 : 209-212, 2001

26 Farquhar-Smith WP, "Administration of endocannabinoids prevents a referred hyperalgesia associated with inflammation of the urinary bladder" 94 : 507-513, 2001

27 Farquhar-Smith WP, "A novel neuroimmune mechanism in cannabinoid-mediated attenuation of nerve growth factor-induced hyperalgesia" 99 : 1391-1401, 2003