Round table 3

In attendance: Nicolas, Philippe, Sarret's lab.

During the recent weekly lab meeting held by Dr. Sarret and his lab, I presented my draft for the prologue, and I outlined how I imagined the breakdown of the rest of the animation would look like. We had a discussion, and I went back to the drawing board (aka Pages). So, here's a very bare-bones script. Soft tissue to come later...

ACT ONE

"Osteoid Pathophysiology"

We will begin showing osteoblast and osteoclast function. Then, introduce cancer factors that alter both cell types. Note, however, that osteoclasts will be the main protagonists/antagonists of the story.

We first start with those that alter osteoclasts directly. We begin to see increased activity and numbers. Then, we see osteoblasts being modulated by factors causing an increase in RANKL expression. This then also increases osteoclast activity.

An osteoclast steps into view, and we end up in its cytoplasm very briefly. We see vesicles and stuff, and protons being pumped out of the cell. Zooming back, we reveal the ruffled border of the osteoclast and see it in action. We then zoom out to see some damage. Exposed nerve endings, and acidic environment.

ACT TWO

"Nociception"

Exposed nerve endings are now susceptible to mechanical stress. Show how.

Inflammatory cells appear. They release factors. Follow the inflammatory cell to the cancer mass surface. See the cancer cells release their own factors.

Follow these factors to the nerve endings. Increased firing.

ACT THREE

"Acidosis and Peripheral Sensitization"

Activated nerves are further aggravated by acidic environment. See allosteric shift in receptors. Show this by following a few protons.

Elaborate on firing frequency and amplitude.

EPILOGUE

"Allusions to Central Sensitization"

One thing that I'm working out now, is that nerve fibres are found surrounding the vessels within the bone cavity. These fibres are in the marrow and lie close to the trabecular surface, but is not in it. On the other hand, the nerve fibres in the compact bone, become exposed only after the resorption process has started. The narration and flow of the current dialogue seems to imply that pain only occurs once the nerve endings in the resorbed bone is revealed.

Indeed, bone resorption occurs simultaneously as tumour growth itself. Temporally, therefore, the nerve ending within the bone may technically be responsible for initial pain symptoms. Nevertheless, I feel we are neglecting the fact that pain can occur first by other means. That is, nociceptor activation may first occur by compression of nerve fibres around marrow vasculature, and by the binding of cancer factors into the marrow cavity.

I feel I need to discuss this further.