Table 2.

Examples of reported neutrophil-dependent hyperalgesia.

Manipulation	Species	Effect on Neutrophils	Type of Hyperalgesia Tested	Method of Neutrophils Reduction	Effect of Neutrophils Reduction	Reference
Leukotriene B4 injected into the dorsum of the paw	Rat	A known potent PMN chemotactic agent	Mechanical hyperalgesia (paw pressure threshold)	Hydroxyurea or methotrexate	Decreased hyperalgesia	(Levine et al., 1984)
N-formyl- methionyl-leucyl-phenylalanine or C5a into the dorsum of the paw	Rat	A known potent PMN chemotactic agents	Mechanical hyperalgesia	Hydroxyurea	Decreased hyperalgesia	(Levine et al., 1985)
Intraplantar nerve growth factor	Rat	Increased MPO activity in plantar skin	Thermal hyperalgesia	Anti-rat PMN	Decreased hyperalgesia	(Bennett et al., 1998)
Partial sciatic nerve ligation	Rat	PMN accumulation in sciatic nerve	Thermal hyperalgesia	Anti-rat PMN	Decreased hyperalgesia	(Perkins and Tracey, 2000)
Allergen (ovalbumin) into the paw	Rat	PMN accumulation in plantar skin	Thermal hyperalgesia	Fucoidin or anti-rat PMN	Decreased hyperalgesia	(Lavich et al., 2006)
Serotonin into the dorsum of the paw	Rat	ND	Mechanical hyperalgesia	Fucoidin	Decreased hyperalgesia	(Oliveira et al., 2007)
Carrageenan into the paw	Rat	Increased MPO activity in plantar skin	Mechanical hyperalgesia	Fucoidin	Decreased hyperalgesia	(Cunha et al., 2008)
Antigen (methylated bovine serum albumin) into knee joint	Mouse	Increased MPO activity in knee joint	Mechanical hyperalgesia	Reparixin or DF2162	Decreased hyperalgesia	(Coelho et al., 2008)
C5a, zymosan, or carrageenan into paw	Rat	Increased MPO activity in paw	Mechanical hyperalgesia	Vinblastine	Decreased hyperalgesia	(Ting et al., 2008)
Partial sciatic nerve ligation	Mouse	PMN accumulation in sciatic nerve	Mechanical hyperalgesia	Anti-Ly6G	Decreased hyperalgesia	(Nadeau et al., 2011)
Intraplantar IL-17	Mouse	PMN accumulation in plantar skin	Thermal hyperalgesia	Fucoidin	Decreased hyperalgesia	(McNamee et al., 2011)
Monosodium urate into the tibio-femoral joint	Mouse	Increased MPO activity in periarticular tissue	Mechanical hyperalgesia	DF2162 or Fucoidin or 5-LOX inhibitor	Decreased hyperalgesia	(Amaral et al., 2012)
Paw incision	Mouse	Increased MPO activity in plantar tissue	Mechanical hyperalgesia	Anti-Ly6G or vinblastine or Ladarixin	Decreased hyperalgesia	(Carreira et al., 2013)
MOG35–55 subcutaneously (causing EAE)	Mouse	PMN accumulation in DRG	Mechanical hyperalgesia	Anti-Ly6G	Decreased hyperalgesia	(Harada et al., 2019)
MOG35–55 subcutaneously	Mouse	PMN accumulation in DRG	Mechanical hyperalgesia	Anti-Ly6G	Decreased hyperalgesia	(Zhang et al., 2019)
Monosodium urate or IL-33/ST2	Mouse	Increased MPO activity	Mechanical hyperalgesia	Fucoidin	Decreased hyperalgesia	(Yin et al., 2020)

Carrageenan, an extract from a red seaweed; EAE, experimental autoimmune encephalomyelitis; Fucoidin, a nonspecific selectin inhibitor; Ladarixin, a CXCR1/2 antagonist; 5-LOX, 5-lipoxygenase, which produces leukotriene B4; MOG, myelin oligodendrocyte glycoprotein; MPO, myeloperoxidase; ND, not determined; PMN, although PMN refers to all granulocytes, it is used here to refer specifically to neutrophils; Reparixin and DF2162, both CXCR1/2 inhibitors; ST2, suppression of tumorigenicity/IL-33 receptor.